ポスター
E. 行動の分子・神経的基盤 2
E. Molecular and Neuronal Bases of Behavior 2 |
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| 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-073
報酬を基にした柔軟な意思決定における、サル前頭眼窩野－尾状核および視床MD核経路の異なる役割
Distinct roles of pathways from monkey orbitofrontal cortex to caudate nucleus and mediodorsal thalamus in value-based adaptive decision-making
*小山 佳(1)、間島 慶(2)、永井 裕司(1)、堀 由紀子(1)、平林 敏行(1)、Mark A G Eldridge(3)、宮川 尚久(1)、三村 喬生(1)、藤本 敦(1)、井上 謙一(4,5)、Richard C Saunders(3)、高田 昌彦(4)、八幡 憲明(2)、八幡 憲明(2)、樋口 真人(1)、Barry J Richmond(3)、南本 敬史(1)
1. 量子科学技術研究開発機構 脳機能イメージング研究部、2. 量子科学技術研究開発機構 量子生命科学領域
*Kei Oyama(1), Kei Majima(2), Yuji Nagai(1), Yukiko Hori(1), Toshiyuki Hirabayashi(1), Mark A G Eldridge(3), Naohisa Miyakawa(1), Koki Mimura(1), Atsushi Fujimoto(1), Ken-ichi Inoue(4,5), Richard C Saunders(3), Masahiko Takada(4), Noriaki Yahata(2), Noriaki Yahata(2), Makoto Higuchi(1), Barry J Richmond(3), Takafumi Minamimoto(1)
1. Dept Func Brain Img, QST, 2. Quan Life Sci, QST, 3. Lab Neuropsychol, NIMH, Bethesda, USA, 4. Sys Neurosci, Prim Res Inst, Kyoto Univ, 5. PRESTO
Keyword: decision-making, monkey, chemogenetics, prefrontal cortex
To survive in a dynamically changing world, animals must rapidly adapt to novel environments and optimize their behavior to maximize rewards. The primate orbitofrontal cortex (OFC) contributes to such reward-based adaptive decision-making by interacting with the caudate nucleus (CD) and the mediodorsal thalamus (MD). However, the causal contributions of these OFC-subcortical pathways remain unidentified in primates. In this study, using chemogenetic technique, Designer Receptors Exclusively Activated by Designer Drugs (DREADDs), we reversibly inactivated OFC and its projection to CD or MD in macaque monkeys. Two monkeys received injections of adeno-associated virus vector expressing inhibitory DREADD, hM4Di, into OFC bilaterally. The monkeys were tested with two versions of modified reversal learning tasks, in which the monkeys were required to choose either of the two visual stimuli presented out of five stimuli. Each stimulus was associated with 1, 2, 3, 4, or 5 drops of juice, and the combination was reversed within a session. In a ‘NOVEL’ task, a new set of visual stimuli was introduced in every session, which required the monkeys to learn novel stimulus-reward associations and then adapt to its reversal. In a ‘FAMILIAR’ task, a fixed set of five visual stimuli was used throughout the experiments so that the monkeys became familiar with the reversal. Silencing of OFC through systemic injection of a DREADDs agonist did not impair initial learning, but did severely impair reversal learning in the NOVEL task. In the FAMILIAR task, the OFC silencing significantly impaired the post-reversal performance. We then conducted pathway-selective silencing by local agonist infusion into either CD or MD. Silencing of the OFC-CD pathway impaired the post-reversal performance in the NOVEL task, but not in the FAMILIAR task. Conversely, silencing of the OFC-MD pathway produced only a slight delay in reversal learning in the NOVEL task, but markedly affected the post-reversal performance in the FAMILIAR task. Reinforcement learning models clearly explained these behavioral deficits, revealing that the OFC-CD pathway is important for updating the reward value in a model-free fashion, while the OFC-MD pathway is critical for quick adaptation of the rule change in a model-based fashion. The present results suggest that the primate OFC-subcortical pathways play distinct roles in reward-based adaptive decision-making when updating the previously learned value. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-074
脳内報酬神経回路が構成するプロスペクト理論を実現するモデル
A neuronal prospect theory model in the brain reward circuitry
*山田 洋(1)、坪 泰宏(3)、今泉 優理(4)、松本 正幸(1)、Agnieszka Tymula(2)
1. 筑波大学医学医療系、2. シドニー大学経済学部、3. 立命館大学 情報理工学部、4. 筑波大学医療科学類
*Hiroshi Yamada(1), Yasuhiro Tsubo(3), Yuri Imaizumi(4), Masayuki Matsumoto(1), Agnieszka Tymula(2)
1. Faculty of Med,Univ of Tsukuba, 2. School of Econ, Univ of Sydney, 3. Ritsumeikan University, College of Information Science and Engineering, 4. Med Sciences, Univ of Tsukuba
Keyword: prospect theory, monkey, utility, probability weighting
Prospect theory is the dominant theory of choice in behavioral economics, but it remains elusive whether the theory is only descriptive of human behavior or has a deeper meaning in the sense that it also describes an underlying neuronal computation that extends to our close evolutionary relatives. Previous human neuroimaging studies have demonstrated that neural responses to rewards measured through blood oxygen levels can be described using prospect theory, but with limited resolution in temporal and spatial domains. How the activity of individual neurons, a possible computational unit, reflects prospect theory remains unknown. Here, we show with theoretical accuracy equivalent to that of human neuroimaging studies that single-neuron activity in four core reward-related cortical and subcortical regions represents the subjective valuation of risky gambles in monkeys. We showed that the activity of individual neurons in the reward circuitry (Dorsal striatum, DS; Ventral Striatum, VS; central part of the orbitofrontal cortex, cOFC) of monkeys perceiving a lottery can be captured based on the prospect theory model as a multiplicative combination of utility and probability weighting functions. One pivotal question is how these various subjective preference signals are transformed into behavioral choices through information processing via neural networks. Our clustering analysis of the parameterized neuronal activity revealed that these signals were similarly distributed across the VS, DS, and cOFC. Our minimal rate model of a three-layered network successfully reconstructed the internal valuation of risky rewards observed in monkeys, suggesting that these subjective valuation signals in the reward circuitry are integrated into the brain to construct a decision output from risky perspectives. Thus, distributed neural coding explains the computation of subjective valuations under risk. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-075
非明示的な課題ルールに基づいた報酬予測を実現するための神経基盤
A neuronal basis underlying reward prediction based on hidden task rules
*吉澤 知彦(1,2,3,4)、宮村 裕人(2,3)、越智 祐太(3)、平 理一郎(2)、舩橋 誠(1)、酒井 裕(4)、崔 翼龍(3)、礒村 宜和(2,3,4)
1. 北海道大学 大学院歯学研究院 口腔機能学分野 口腔生理学教室、2. 東京医科歯科大学 大学院医歯学総合研究科 細胞生理学分野、3. 理化学研究所 生命機能科学研究センター 生体機能動態イメージング研究チーム、4. 玉川大学 脳科学研究所
*Tomohiko Yoshizawa(1,2,3,4), Yuuto Miyamura(2,3), Yuta Ochi(3), Riichiro Hira(2), Makoto Funahashi(1), Yutaka Sakai(4), Yilong Cui(3), Yoshikazu Isomura(2,3,4)
1. Oral Phys, Dep Oral Func Sci, Grad Sch Dent Med, Hokkaido Univ, Hokkaido, Japan, 2. Dept Physiol and Cell Biol, Grad Sch Med and Dent Sci, Tokyo Med and Dent Univ, Tokyo, Japan, 3. Lab Biofunction Dynamics Imaging, RIKEN BDR, Hyogo, Japan, 4. Brain Sci Inst, Tamagawa Univ, Tokyo, Japan
Keyword: DOPAMINE, REWARD PREDICTION ERROR (RPE), STRIATUM, HIDDEN STATE
If there are hidden rules in the environment, animals can survive more by choosing their behavior according to those rules. However, the neuronal basis for recognizing the rules and changing behavior based on them is not well understood.
To address this question, we compared rat's whole-brain activities during two different tasks: one in which an operant behavior is alternately rewarded (alternate-reward task) and another in which the same operant behavior is randomly rewarded with a 50% probability (random-reward task). The 2-deoxy-2-[18F]fluoro-D-glucose -positron emission tomography (18F-FDG-PET) revealed that the ventral tegmental area (VTA) was more strongly activated by the alternate-reward task than by the random-reward task.
Since the VTA is one of the major sources of dopaminergic neurons encoding reward-prediction error (RPE), we recorded neuronal responses to alternate, random and 100% rewards from head-fixed rats performing a similar task to the PET experiment by using an electrophysiological technique. Some neurons more weakly responded to alternate rewards than to random rewards, reflecting the alternation nature. The others showed similar responses to both alternate and random rewards, reflecting the 50% reward probability. The prediction of reward is more accurate to 100% rewards than to random rewards, and the accuracy to alternate rewards is somewhere in between the two. We normalized so that the amplitude of response to the random reward was 1 and one of response to the 100% reward was 0, then got relative amplitude of response to the alternate reward. The relative amplitude was negatively correlated with medial-lateral coordinate of the recorded neurons.
The lateral and medial VTA neurons mainly project to the dorsomedial striatum (DMS) and the nucleus accumbens (NAc) respectively, thus we measured dopamine (DA) dynamics in these areas from head-fixed mice performing a similar task to rat's experiments by using fiber photometry recording of dLight1.1. In the DMS, phasic DA release to alternate rewards was smaller than to random rewards, whereas in the NAc, difference of phasic DA releases to alternate and random rewards were smaller than in the DMS, indicating that DA dynamics in the DMS more strongly reflected the alternation nature than in the NAc. These results suggests that dopaminergic projection to the DMS is one of the neuronal bases underlying reward prediction based on hidden task rules. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-076
青斑核ノルアドレナリンニューロンによるスキーマに基づく行動の調節
Locus coeruleus noradrenergic control of schema-based behavior in contingency reversal
*雨宮 誠一朗(1)、Thomas McHugh(1)
1. 理化学研究所脳神経科学研究センター
*Seiichiro Amemiya(1), Thomas McHugh(1)
1. RIKEN Center for Brain Science
Keyword: locus coeruleus, noradrenaline, schema, decision making
In decision making the inferential process that allows the deliberation and anticipation of current state and possible outcomes requires schema, knowledge structure of task and environment. Thus, the context-dependent reference and manipulation of schema is crucial for adaptive behavior and decision making, however, its neural mechanism is still unclear. Previous studies have reported that locus coeruleus noradrenergic neurons (LC-NA) are involved in controlling cognitive processes such as memory, attention and decision making in accordance with current demands, suggesting LC-NA may play a role in schema-related processes. Here, we examined the involvement LC-NA in schema-based inference by combining reversal learning paradigms in the T-maze with chemogenetic inhibition of activity of LC-NA in mice. Inhibitory Gi DREADD (designer receptor exclusively activated by designer drug) receptors were expressed in LC-NA and subject mice were trained a maze task where reward contingency (correct side has 2 pellets at 90%, and incorrect side was not rewarded) switched multiple times (every 15-25 correct trials) in each session for three weeks; enhanced correct choice across the training indicated mice established schema of the task. After training, mice ran same task following daily injection of the DREADD ligand deschloroclozapine (DCZ) or saline as control. Inhibition of LC-NA, compared to the control condition, increased correct choices 15 trials after the reversal as a result of persistent choice of the correct side, indicating the inhibition of LC-NA suppressed predictive choices mediated by schema-based inference of contingency reversal. Next, we examined effect of inhibition of LC-NA on learning a new schema. Mice were trained on a T-maze with one arm baited with 3 pellets and the other baited with 1 for four consecutive days, then the reward condition was reversed and mice ran the reversal condition for six consecutive days. LC-NA inhibition impaired learning of the high reward side both during the initial learning and following reversal and decreased mice’s head orienting behavior (“vicarious trial-and-error” (VTE)) at the choice point which reflect schema-based deliberation, indicating the inhibition LC-NA impaired schema learning and manipulation. Together, our data suggest that LC-NA plays a role in schema-based processes. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-077
マウスの音弁別課題における皮質背側領域の役割
Contribution of dorsal cortical regions in mouse auditory perceptual decision-making task
*畑 覚真(1,2)、船水 章大(1,2)
1. 東京大学大学院総合文化研究科、2. 東京大学定量生命科学研究所
*Kakuma Hata(1,2), Akihiro Funamizu(1,2)
1. Grad Sch Arts and Science, Univ of Tokyo, Tokyo, Japan, 2. Institute for Quantitative Biosciences, Univ of Tokyo, Tokyo, Japan
Keyword: DECISION MAKING, CORTEX, AUDITORY PERCEPTION, OPTOGENETICS
When sensory inputs are uncertain, the ability to infer the environmental state by using prior knowledge of rewards and stimulus probabilities is essential for adaptive behavior. Our previous study (Funamizu, 2021) found that mice integrated sensory inputs and prior knowledge to optimize choices and changed the behavior based on sensory uncertainty. Although some studies report that multiple regions in the cerebral neocortex (e.g., posterior parietal cortex, entorhinal cortex, and frontal cortices) are involved in the reward- and sensory-based decision making, it is still unclear how these regions in the neocortex are orchestrated and make Bayesian action selection. Here we utilize photostimulation in a previous study (Guo et al., 2014) and inactivate each region of dorsal neocortex in the VGat-ChR2 mice during a behavioral task. Since the VGat-ChR2 mice expressed channelrhodopsin-2 (ChR2) in GABAergic interneurons, a blue laser produced local inactivation of cortex. Our behavior task required head-fixed mice to choose between the right or left spout associated with the high or low tone frequency. Compared to our previous task (Funamizu, 2021), we only used the sound stimulus of 0.6 sec and did not bias the reward amount of left and right choices. Consistent with the previous study (Guo et al., 2014), lateralized inactivation of the anterior lateral motor cortex (ALM) made the mice choose the ipsilateral side of inactivation. Also, inactivation of the auditory cortex (AC) had a similar effect to the choices, suggesting that the ALM and AC are involved in the contralateral choice. Further experiments with various sound durations and reward biases in our task would provide how the neocortex is involved in the integration of sensory inputs and prior knowledge. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-078
制限時間依存的な意思決定戦略切替えメカニズムを研究するためのサルの新規採餌課題
Novel foraging task for studying decision strategy switching under different time constraints in monkeys
*石井 宏憲(1)、中村 加枝(1)
1. 関西医科大学
*Hironori Ishii(1), Kae Nakamura(1)
1. Kansai Medical University
Keyword: foraging, monkey, decision making, reward
We change a decision strategy according to the expected reward and the time limit. To maximize rewards under a strict time constraint, one would pursue a quick and efficient strategy different from those when enough time is available. The neural mechanisms of such strategy switching based on the given time are largely unknown. Here we developed a new behavioral paradigm to test foraging strategy under different time constraints in monkeys. The task is to collect as many rewards scattered along the one-way route as possible within a time limit. The monkey faced with a panel equipped with 25 buttons positioned in 5×5 space (served as “reward” buttons) and two buttons placed next to both left and right ends of the middle row (served as “start” and “goal” buttons). After pressing the start button, one reward button in each column illuminated such that a total of 5 reward buttons were presented simultaneously. The illumination color of one out of the five buttons was different, indicating that the reward related to this button tripled more than the others. The monkey sequentially selected the reward buttons or might skip some of them. Collected rewards were given by the number of water drops after reaching the goal button within a time limit. We tested four conditions of the time limit (3s, 4s, 5s, and no limit, indicated by LED color of the start button) with a block-design session (N=10). We demonstrated that a monkey (Macaca fascicularis, male) successfully optimized the foraging behavior according to the time constraints; the overall proportion of the time limit break error was less than 10% even at the 3 s limit condition. The monkey increased the number of skips as the time limit became shorter: the averages were 0.5 at no limit, 0.7 at 5s, 1.6 at 4s, 1.8 at 3s. Average foraging times decreased as the time limit became shorter: 3.3 s at no time limit, 2.9 s at 5 s, 2.4 at 4s, 2.1 s at 3 s, indicating that the monkey shorten the foraging time fast enough to complete a trial in a limited time. Logistic regression analysis revealed that the size of the reward had more significant, and the distance had fewer impacts on choice during the condition when in shorter time limits waswere imposed. The results indicate that this foraging task is suitable for studying how animals construct foraging strategies with different values and distances of individual rewards under different time constraints, to maximize a total gain. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-079
スキル獲得過程における線条体後部活動
Neuronal representations in the posterior striatum during the acquisition process of skill
*谷本 彩(1,2)、藤澤 茂義(1,2)
1. 理化学研究所脳神経科学研究センター、2. 東京大学大学院新領域創成科学研究科
*Sai Tanimoto(1,2), Shigeyoshi Fujisawa(1,2)
1. RIKEN CBS, Saitama, Japan, 2. Grad Sch Front Sci, Univ of Tokyo, Chiba, Japan
Keyword: skill learning, electrophysiology, posterior striatum
Animals have to choose appropriate actions as quickly as possible to forage for food or to escape from predators. The abilities to find something familiar to the animals and to move quickly toward it are called ‘object skill’ and ‘motor skill,’ respectively. Both types of skill are acquired by repeatedly experiencing the same situation. Recent studies have revealed that the former object skill is supported by the posterior striatum, which is highly innervated from various sensory-related regions. In this study, we investigated how the representation of stimuli in the posterior striatum is shaped in the acquisition process of object skill, and how the activities of the posterior striatum are orchestrated with the sensory cortices and thalami. First, we developed a two-alternative forced-choice task using a T-shaped apparatus. In this task, we presented two types of images (black or white) on the screens placed on both sides of the central aisle. Since the central aisle was wide and long enough for rats to change their path before they reached the T-junction, we estimated the position that the rats shifted to the left or the right, referred to as judgement distance. Reward water ports were set on both arms of the T-maze, and rats got reward water when they chose the correct arm. After several sessions for training, the rats (n=4) learned to discriminate the images to choose the correct arm, which reflected in success rate > 80%. Reaction time, defined as the time to take from the start position to either arm of the T-maze, decreased steadily, and the judgement distance was also shortened as learning progressed. These behavioral results suggest that the rats gradually acquired object skill for visual discrimination across sessions in the task. Then, we recorded the neural activities extracellularly using silicon probes from the visual striatum (posterior striatum), the visual cortex, and the visual thalamus (dorsolateral geniculate nucleus) simultaneously while the rats performed the task. We found that a certain amount of neurons in these areas exhibited judgement-related (either left or right) and/or task-phase-related (such as visual stimulus onset and offset and reward timing) activities. Our results indicate the involvement of the neuronal activities of the visual striatum, visual cortex, and visual thalamus in learning the visual discrimination task. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-080
混合戦略ゲームと事象関連電位
Event-related potentials during decision-making in a mixed-strategy game
*小林 俊輔(1)、Chang Fang-Yu(2)、Wiratman Winnugroho(3)、宇川 義一(4)
1. 帝京大学医学部神経内科、2. 福島県立医科大学神経内科、3. インドネシア大学神経内科、4. 福島県立医科大学ヒト神経生理学講座
*Shunsuke Kobayashi(1), Chang Fang-Yu(2), Wiratman Winnugroho(3), Ugawa Yoshikazu(4)
1. Dept Neurology, Teikyo University, Tokyo, Japan, 2. Dept Neurology, Fukushima Medical University, Fukushima, Japan, 3. Dept Neurology, Universitas Indonesia, Jakarta, Indonesia, 4. Dept Human Neurophysiology, Fukushima Medical University, Fukushima, Japan
Keyword: dopamine, game theory, readiness potential, high-density EEG
The decisions we make are sometimes influenced by interactions with other agents. Previous studies have suggested that the prefrontal cortex plays an important role in decision-making and that the dopamine system underlies processes of motivation, motor preparation, and reinforcement learning. However, the physiological mechanisms underlying how the prefrontal cortex and the dopaminergic system are involved in
decision-making remain largely unclear. The present study aimed to determine how decision strategies influence event-related potentials (ERPs). We also tested the effect of levodopa, a dopamine precursor, on decision-making and ERPs in a randomized double-blind placebo-controlled investigation. The subjects performed a matchingpennies task against an opposing virtual computer player by choosing between right
and left targets while their ERPs were recorded. According to the rules of the matchingpennies task, the subject won the trial when they chose the same side as the opponent, and lost otherwise. We set three different task rules: (1) with the alternation (ALT) rule, the computer opponent made alternating choices of right and left in sequential trials; (2) with the random (RAND) rule, the opponent randomly chose between right and
left; and (3) with the GAME rule, the opponent analyzed the subject’s past choices to predict the subject’s next choice, and then chose the opposite side. A sustained medial ERP became more negative toward the time of the subject’s target choice. A biphasic potential appeared when the opponent’s choice was revealed after the subject’s response. The ERPs around the subject’s choice were greater in RAND and GAME than in ALT, and the negative peak was enhanced by levodopa. In addition to these medial ERPs, we observed lateral frontal ERPs tuned to the choice direction. The signals emerged around the choice period selectively in RAND and GAME when levodopa was administered. These results suggest that decision processes are modulated by the dopamine system when a complex and strategic decision is required, which may reflect decision updating with dopaminergic prediction error signals. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-081
部分観測迷路探索中のシーン予測デコーダビリティの差異と確信度
Confidence modulates the decodability of scene prediction during partially-observable maze exploration
*片山 梨沙(1,4)、吉田 和子(2,3)、石井 信(1,4,5)
1. 京都大学 情報学研究科、3. （株）国際電気通信基礎技術研究所 数理知能研究室、4. （株）国際電気通信基礎技術研究所 脳情報解析研究所、5. 東京大学 ニューロインテリジェンス国際研究機構
*Risa Katayama(1,4), Wako Yoshida(2,3), Shin Ishii(1,4,5)
1. Grad. Sch. of Info., Kyoto Univ., Kyoto, Japan, 2. Univ. of Oxford, Nuffield Dept. of Clinical Neuroscience, Oxford, UK, 3. Dept. of Neural Computation for Decision-making, ATR Institute International, Kyoto, Japan, 4. Neural Information Analysis Labs, ATR Institute International, Kyoto, Japan, 5. IRCN, the Univ. of Tokyo, Tokyo, Japan
Keyword: Prediction, Confidence, Belief inference, Multi-voxel pattern analysis
Prediction ability often involves some degree of uncertainty—a key determinant of confidence. In reality, environmental uncertainty must be dynamically resolved by continuously incorporating new information into the decision-making process. However, the relationship between the decodability for predictions and confidence, whose changes are associated with such uncertainty resolution, has never been assessed. Here, we sought to assess whether the prediction decodability in partially-observable environments, where one’s state is uncertain, is sensitive to confidence produced by such uncertainty.
We used functional magnetic resonance imaging (fMRI)-based, partially-observable maze exploration tasks. In this task, subjects explored the pre-learned grid maze from an unknown initial state and predicted the upcoming scene during the exploration. To successfully perform the task, subjects needed to infer their current state in the maze based on the history of actions (i.e., moving directions) and previously observed scenes. We assessed the confidence level in their beliefs about where they were in the maze (state confidence) using a hidden Markov model of the subjects’ maze exploration behaviors.
Our HMM-based behavioral model allowed us to successfully estimate subjects’ state confidence, although it was not explicitly reported in the experiment. Using a multi-voxel pattern analysis (MVPA), we successfully decoded the subjects’ scene predictions and their state confidence level from activities in the localized parietal and prefrontal regions. Importantly, our model-based MVPA revealed that scene prediction decodability showed highly significant difference according to the state confidence level in the inferior parietal lobule (IPL).
This study demonstrated that the localized neural representations of future scene predictions during partially-observable maze exploration differed depending on the confidence level of the current state inference, which functions as upstream information processing of the upcoming scene prediction. Our ROI-based MVPA results also suggested that the IPL may be related to the neural representation of state inference. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-082
感覚領野 - 判断関連領野間のβ帯域同期振動は課題に関係ない機能結合の抑制に関連している
Synchronous beta-band oscillation between sensory and decision related areas is related to inhibition of task-irrelevant functional connection
*須田 悠紀(1)、宇賀 貴紀(1)
1. 山梨大学大学院総合研究部医学域
*Yuki Suda(1), Takanori Uka(1)
1. Grad Sch Med, Univ of Yamanashi, Yamanashi, Japan
Keyword: beta-band oscillation, MT, LIP, decision making
Flexible behavior based on multiple rules is a fundamental ability for humans. Neurons in the lateral intraparietal area (LIP) accumulate relevant information preferentially depending on context, but, how sensory information represented in visual cortex, area MT, is conveyed to stages of evidence accumulation remains unclear. To elucidate this question, we investigated the functional connectivity between MT and LIP by recording simultaneously from both areas using two electrodes while monkeys performed a switching task.
A Japanese macaque was trained to flexibly switch between a direction discrimination task and a depth discrimination task. Difficulty of the tasks was varied by changing the percentage of coherently moving and binocularly correlated dots in a random dot stimulus. We recorded local field potential (LFP) in areas MT and LIP simultaneously with two single-contact electrodes. The preferred choice target was placed toward the response field of the LIP neuron, whereas the anti-preferred target was positioned diametrically opposite to the preferred target. The random dot stimulus which was optimized to the preference of the MT neurons was presented in the receptive field of the neurons.
To examine functional connectivity, we calculated pairwise phase consistency (PPC) between the two electrodes. We found that beta-band oscillation had a peak around 200ms after visual stimulus onset, and decayed at saccadic eye movement. Granger causality analysis demonstrated that the beta-band oscillation had a direction from area LIP to MT, suggesting that the beta-band synchrony might be due to a top-down signal related to context-dependent decision making. To examine whether the oscillation depended on task relevance, we grouped the MT-LIP pairs into “task-relevant” and “task irrelevant” pairs where the former was task relevant in that the preference of the MT neuron coincided with the response field of the LIP neurons, and the latter was task irrelevant in that the preferences were incongruent for making a correct decision. The beta-band oscillation for task irrelevant pairs was significantly larger than that for task relevant pairs during decision formation.
These results suggest that the beta-band top-down oscillation from area LIP to MT might be related to inhibition of task-irrelevant connection for achieving flexible decision making. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-083
成魚ゼブラフィッシュの学習と意思決定における外套と外套下部に投射するセロトニンニューロン軸索の活動と機能の差異
The difference of activities and functions of serotonergic axons in dorsal pallium and subpallium for learning and decision-making of adults zebrafish.
*柴山 康太郎(1,2)
1. 理化学研究所 脳神経科学研究センター、2. 東京大学大学院 総合文化研究科
*Kotaro Shibayama(1,2)
1. RIKEN CBS, 2. University of Tokyo, Graduate School of Arts and Sciences
Keyword: Zebrafish, Serotonin
In vertebrate, the raphe serotonergic neurons are implicated in multiple brain function such as motor behaviors, motivation, and learning. There are several subtypes of raphe serotonergic neurons depending on their locations, projecting regions, and gene expressions, and they play different roles. Due to their complicated subtypes, it is difficult to reveal their functions. Zebrafish is a powerful model animal, because they have a small and simple brain. However, adults zebrafish have the evolutionary homologs of mammalian cortex, limbic system, and basal ganglia in telencephalon. For this advantage, we established a close-loop virtual reality Ca2+ imaging system for adult zebrafish dorsal pallium, which is the homologs of mammalian cortex and limbic system (Torigoe et al., 2021). In this system, zebrafish learn GO/NOGO task for escaping electrical shocks. Recently our laboratory developed a new imaging system which can detect the neural activity in sub-pallium, which is the homologs of mammalian basal ganglia. We used this imaging system for measuring the neural activity of serotonergic axon in telencephalon. We found that the serotonergic axonal activities in dorsal pallium and sub-pallium were different. The serotonergic axons in dorsal pallium were suppressed by both dangerous color and safe color at the earliest stage of GO/NOGO task learning. As the learning trials were repeated, the axons keep being suppressed when zebrafish was in dangerous region but turned to be activated when in safe region even before zebrafish learn GO/NOGO task completely. This tendency of activity was seen after learning. From these results, the axons encoded the value of color rapidly and in dorsal pallium, i.e. rules of environment. Therefore, the serotonergic axons in dorsal pallium may be involved in the establishment of visual learning quickly. On the other hand, the axons in sub-pallium were strongly activated by electrical shocks as the outcome of failure trials. Besides, the axons were tonically activated when zebrafish successfully performed GO-task, in which shock predictive cues were presented. This activity pattern was similar to striatal neurons located in subpallium, which encode prediction of a specific ideal sensory state (Tanimoto et al., this meeting). | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-084
報酬獲得戦略の光遺伝学的脳回路調節
Optogenetical adjustment of the balance between risky and safer decision
*佐々木 亮(1)、太田 安美(2)、尾上 浩隆(3)、山口 玲於奈(4)、德田 崇(5)、伊佐 かおる(1)、高橋 淳(6)、小林 憲太(7)、太田 淳(2)、伊佐 正(1,3,4)
1. 京都大学大学院医学研究科、2. 奈良先端科学技術大学院大学 先端科学技術研究科、3. 京都大学大学院医学研究科 脳機能総合研究センター、4. 京都大学高等研究院ヒト生物学高等研究拠点、5. 東京工業大学科学技術創成研究院、6. 京都大学iPS細胞研究所CiRA、7. 大学共同利用機関法人 自然科学研究機構 生理学研究所
*Ryo Sasaki(1), Yasumi Ohta(2), Hirotaka Onoe(3), Reona Yamaguchi(4), Takashi Tokuda(5), Kaoru Isa(1), Jun Takahashi(6), Kenta Kobayashi(7), Jun Ohta(2), Tadashi Isa(1,3,4)
1. Division of Physiology and Neurobiology, Department of Neuroscience, Graduate School of Medicine, Kyoto University, Kyoto, 606-8501, Japan, 2. Division of Materials Science, Graduate School of Science and Technology, Nara Institute of Science and Technology, 8916-5 Takayama, Ikoma, Nara, 630-0192, Japan , 3. Human Brain Research Center, Graduate School of Medicine, Kyoto University, Kyoto, 606-8507, Japan, 4. Institute for the Advanced Study of Human Biology (WPI-ASHBi), Kyoto University, 606-8501, Japan , 5. Institute of Innovative Research, Tokyo Institute of Technology, Meguro-Ku, Tokyo, 152-8550, Japan, 6. Department of Clinical Application, Center for iPS Cell Research and Application, Kyoto University, Kyoto 606-8507, Japan, 7. Section of Viral Vector Development, National Institute for Physiological Sciences, Okazaki 444-8585, Japan
Keyword: Decision making, Optogenetics, Neural recordings, macaque monkey
Humans encounter situations where they are forced to choose an action with either high risk but high return (HH = risky choice) or low risk and low return (LL = safer choice). Decisions are basically made depending on their situation such as how much their money stock remains (in case of investment) or whether they are winning/losing a game (in case of gambling). Pathological decision-making is known to underlie the symptoms like gambling disorder. Then, is there any neural systems to adjust the balance between risky and safer decision? We developed a complex multi-dimensional decision-making task (HH-LL task) where macaque monkeys are required to handle risky choices to get reward. We found that selective optogenetical activation of the pathway from ventral tegmental area (VTA) to ventrolateral prefrontal cortex (vlPFC) during the decision period of the task facilitated the risky choices without affecting the expected value-dependency, where risk-preferring α-band cue-responses was enhanced by the photostimulation (Neuro 2021). In this study, we additionally implemented the systematic mapping in the prefrontal cortices (PFCs) by the optogenetic activation of their inputs from the VTA. To clarify the role of dopaminergic inputs to multiple prefrontal areas in this risk-based decision, the terminals of the VTA-PFC pathway were optogenetically activated with LED arrays carrying electrocorticography electrodes. We found electrocorticogram recordings showed that the α-band cue responses in the dorsolateral prefrontal area (dlPFC) was smaller in case of the risky choices than the safer choices. Moreover, interestingly, optogenetic activation of the VTA-dlPFC pathway during the decision period of the task facilitated the safer choices (reduced risky choices) without affecting the expected value-dependency, and inhibited the risk-preferring α-band activity. This is the opposite effect from our past findings of the VTA input to the vlPFC which facilitated the risk-preferring behavior, i.e., the activation of VTA-dlPFC pathway could reduce the risk-preferring behavior. These findings can lead to our further understandings of brain mechanism regarding human decisions between risky and safer choices. It may contribute to develop the therapeutic methods to adjust the balance between the risky and safer choice. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-085
頭部固定マウスでの行動課題による推論型戦略とモデルフリー戦略の切り分け
Dissociation of inference-based and model-free strategy in head-fixed mouse
*王 碩(1,2)、石津 光太郎(2)、船水 章大(1,2)
1. 東京大学大学院総合文化研究科、2. 東京大学定量生命科学研究所
*Shuo Wang(1,2), Kotaro Ishizu (2), Akihiro Funamizu(1,2)
1. Grad Sch Art and Sci, The Univ of Tokyo, Tokyo, Japan, 2. Institu of Quanti Biosci, Univ of Tokyo, Tokyo, Japan
Keyword: DECISION MAKING, INFERENCE-BASED, MODEL-FREE, ELECTROPHYSIOLOGY
Humans and animals not only habitually make decisions based on direct experiences, but also infer a hidden context based on sensory inputs for flexible decisions. The inference-based strategy has an advantage to use the transition of context for action selection, whereas the model-free strategy responds rapidly from the current environment. It is unclear how the two strategies integrate in the brain. Here, we established a tone-frequency discrimination task in head-fixed mice to investigate their selection ability of inference-based and model-free strategies. The task had zigzag- and repeat-condition in which the tone frequency of current trial was controlled by a transition probability from previous trial. Mice selected left or right spout depending on the low or high frequency of sound stimulus to get a water reward. We found that mice biased choices depending on the transition probability of stimulus both in the zigzag- and repeat-conditions. Also, the learning speed of mice in repeat-condition was faster than in zigzag-condition, suggesting that mice had different strategies between the two conditions. Further electrophysiological experiments in our task may provide a neuronal mechanism of inference-based and model-free strategies. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-086
セロトニンによるモデルベース意思決定過程の制御
Serotonergic Control of Model-based Decision Making
*平良 正和(1)、アカム トーマス(2)、ウォルトン マーク(2)、銅谷 賢治(1)
1. 沖縄科学技術大学院大学神経計算ユニット、2. オックスフォード大学実験心理学部
*Masakazu Taira(1), Thomas Akam(2), Mark E. Walton(2), Kenji Doya(1)
1. Neural Computation Unit, OIST, Okinawa, Japan, 2. Department of Experimental Psychology, University of Oxford, Oxford, U.K.
Keyword: SEROTONIN, MODEL-BASED DECISION MAKING, REINFORCEMENT LEARNING, OPTOGENETICS
Serotonin (5-HT) is an essential neuromodulator in reward-driven adaptive behaviors. Recent studies using a two-step decision task under tryptophan depletion in humans and devaluation paradigm in optogenetic mice suggest that 5-HT promotes model-based decision making. Here we took a recently-developed rodent two-step decision task to test the effect of optogenetic inhibition of 5-HT neurons on model-based decision making. In the two-step decision task, mice initiated each trial by nose-poking a center port after it was illuminated. At the first step, mice could then choose between left and right ports. Each first-step choice led to a probabilistic transition to one of two second-step states, e.g., 80% to upper port lit and 20% with lower port lit. By nose poking to the lit port, mice could probabilistically obtain rewards. While the state transition probabilities were fixed for each mouse, the reward probability for upper and lower ports changed in blocks within each session. We trained eight Tph2-ArchT transgenic mice and implanted an optic probe above the dorsal raphe nucleus (DRN). In test trials, photoinhibition by yellow light was applied from the outcome delivery till the first-step choice at the next trial. In control trials, blue light stimulation was applied. Mouse behavior showed that the trial outcome interacted with the common or rare state transition to determine the probability of repeating the choice, consistent with model-based control. The photoinhibition shortened the time to make first-step choices (497.94 ± 20.03 and 482.38 ± 19.23 in control and inhibition trials respectively, p = 4.0x10-5), possibly due to disrupted deliberative model-based decision making. We analyzed the first-step choice behaviors using a model-free/model-based hybrid reinforcement learning model, which used the weighted sum of action values computed by model-free and model-based strategies. Fitting the hybrid model to the choice data showed that photoinhibition decreased the reliance on model-based decision making (weight of model-based strategy: 4.76 ± 0.38 and 4.00 ± 0.45 in control and inhibition trials respectively, p = 0.0054) but not model-free one (weight of model-free strategy: 2.32 ± 0.26 and 2.60 ± 0.24 in control and inhibition trials respectively, p = 0.12), suggesting DRN 5-HT neurons specifically control the use of model-based decision making. These results revealed the role of DRN 5-HT neurons in model-based computation in dynamic environments. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-087
黒質-線条体路ドーパミン伝達による行動関連ニューロン活動の報酬履歴への依存性
Dependence of action-related neuron activity mediated by nigrostriatal dopamine transmission on reward experience
*野々村 聡(1,2)、リオス アライン(1)、加藤 成樹(3)、酒井 裕(4)、南部 篤(5)、高田 昌彦(2)、小林 和人(3)、木村 實(4)、礒村 宜和(1,4)
1. 東京医科歯科大学大学院医歯学総合研究科、2. 京都大学霊長類研究所、3. 福島県立医科大学生体情報伝達研究所生体機能研究部門、4. 玉川大学脳科学研究所、5. 自然科学研究機構生理学研究所システム脳科学研究領域生体システム研究部門
*Satoshi Nonomura(1,2), Alain Rios(1), Shigeki Kato(3), Yutaka Sakai(4), Atsushi Nambu(5), Masahiko Takada(2), Kazuto Kobayashi(3), Minoru Kimura(4), Yoshikazu Isomura(1,4)
1. Department of Physiology and Cell Biology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 2. Primate Research Institute, Kyoto University, 3. Department of Molecular Genetics, Institute of Biomedical Science, Fukushima Medical University, 4. Brain Science Institute, Tamagawa University, 5. Division of System Neurophysiology, National Institute of Physiological Sciences and Department of Physiological Sciences, SOKENDAI
Keyword: Dopamine, Striatum, Action, Reward
Dopamine (DA) projections from the substantia nigra pars compacta (SNc) to the striatum play an important role in action selection based on reward experience by encoding reward prediction error signal (Schultz et al., 1997). According to the conventional theory, phasic DA neuron activity representing reward information excites the direct pathway spiny projection neurons (dSPNs) but inhibits the indirect pathway spiny projection neurons (iSPNs) in the striatum through DA receptors D1R and D2R, respectively, in an antagonistic manner (Kravitz et al., 2012). However, recent studies reported the involvement of such activity in controlling immediate actions rather than responding to reward (Silva et al., 2018) and, also, concurrent action-related activity with similar reward information detected in the dSPNs and iSPNs (Isomura et al., 2013). Thus, there is still a debate about how the phasic activity of those neurons processes such action and reward information via DA.To address this issue, we investigated how differentially action-related neuron activity in the SNc and striatum mediated by the DA transmission represents the information concerning reward experience. We trained rats to perform the push/pull choice task based on the reward experience under head fixation (Nonomura et al., 2018). The rats had to select and execute the adequate action based on reward acquisition or no-reward in past trials. We recorded and isolated the spike activity of SNc and striatal neurons through 64ch silicon probe. In particular, the SNc neurons projecting to the dorsomedial striatum (DMS) (n = 19) and the dorsolateral striatum (DLS) (n = 11), and the iSPNs in the DMS (n = 22) and the DLS (n = 19) were identified by means of antidromic spike detection after optogenetic striatal stimulation of channelrhodopsin (ChR2)-positive DA terminals (tyrosine hydroxylase (TH)-Cre rats with Cre-dependent expression of ChR2 via viral vectors) or optogenetic external pallidal stimulation of ChR2-positive iSPN terminals (Drd2-Cre rats with Cre-dependent expression of ChR2). We obtained the following findings: (1) Action-related activity of SNc neurons positively encoded the reward experience regardless of their projection targets (DMS or DLS); and (2) Action-related activity of the iSPNs also positively reflected the reward experience in both the DMS and the DLS.The present results suggest that the action-related activity of SNc neurons and iSPNs mediated by the mediolaterally-arranged DA transmission may similarly encode reward information. This cannot be explained merely by postulating the inhibitory effect of DA on the iSPNs via D2R and, therefore, may provide a new insight into refinement of the DA system within the basal ganglia. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-088
ジュウシマツにおける状況依存的なさえずり構造の変化
Analyzing context dependent-change of song structure of Bengalease Finch
*藤林 瑞季(1)、河路 琢斗(2,3)、安部 健太郎(2,3)
1. 東北大学理学部生物学科、2. 東北大学高等研究機構、3. 東北大学大学院生命科学研究科
*Mizuki Fujibayashi(1), Takuto Kawaji(2,3), Kentaro Abe(2,3)
1. Faculty of Science,Tohoku University, 2. Division for the Establishment of Frontier Sciences,Tohoku University, 3. Graduate School of Life Sciences, Tohoku University
Keyword: Bengalease Finch, song syntax, context-depent changes, communication
Songs are vocal signals used by songbirds to communicate with others. Songs are composed of sound elements—syllables—weaved into sequences. Some species of songbirds, including the Bengalese finch, use a variety of syllable sequence for communication, but how they utter different songs in a different context remain poorly understood. We have previously developed an experimental system to record and analyze syllable sequences in response to the presentation of virtual information to songbirds. To further explore the role of songs for communication and the neural and developmental mechanism underlying them, we utilize this system to analyze the stimulation-dependent change of syllable sequence in the songs of the Bengalese finch. We found that the presentation of the video-recorded physiological signals evoked changes in their behavioral response according to the stimuli contents. Concerning the ordering of syllables within them, the structure of songs also displayed stimuli-dependent changes. We observed the variability in the persistence of the structural change in songs; some of them were transient, and some were long-lasting for more than a week. Furthermore, the plastic shift in syllable orders tended to occur in the particular transition of syllables. Our results reveal that the Bengalese finch can plastically change the contents of their song according to the social and environmental situation. Our experimental system establishes an efficient method to explore the neural mechanism of how songbirds utilize different songs to convey information. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-089
意味的に対称な情報はヒト脳内において分散的でヘテロな表現を持つ
Distributed, heterogeneous representations of semantically symmetric information in the human brain
*王 佳新(1,2)、ブラン アントワーヌ(1)、西本 伸治(1,2)、西田 知史(1,2)
1. 情報通信研究機構（NICT)、未来ICT研究所、脳情報通信融合研究センター（CiNet)、2. 大阪大学、生命機能研究科
*Jiaxin Wang(1,2), Blanc Antoine (1), shinji nishimoto(1,2), satoshi nishida(1,2)
1. the Center for Information and Neural Networks (CiNet), Advanced ICT Research Institute, NICT., 2. Graduate School of Frontier Biosciences, Osaka University
Keyword: Computational Neuroscience, Language, FUNCTIONAL MRI
Recent evidence suggests that semantic representations associated with thousands of words are distributed across various regions in the human brain (Huth et al., 2012, Neuron; Huth et al.,2016, Nature; Nishida et al., 2021, PLOS Comput.Biol.). These studies have revealed the semantic representations using fMRI-based quantitative modeling (i.e., voxelwise modeling; Naselaris et al., 2011, NeuroImage) based on the structure of semantic similarity between words. However, words have various representational properties beyond similarity, one of which is semantic symmetry. Existing research has used bestowed similarity features that do not enable to visualize the representational structure of semantically symmetric information in the brain. Thus, it is still unclear how semantically symmetric information is represented in the brain. We addressed this issue by using voxelwise modeling to predict fMRI responses to naturalistic movie scenes from 30 semantic labels on the scenes. Each of the 30 labels, which had 15 symmetric pairs (e.g., "intelligent" and "stupid", "urban" and "rural", "amusing" and "gloomy", etc.), was manually evaluated in each scene using the rating on 5-point scales of the label. We confirmed that time series of manual ratings on individual labels showed significantly negative correlation between most of symmetric pair. However, the weight of voxelwise models, which reflects the cortical representation of each semantic label, did not exhibit such a negative correlation even in the same symmetric pair. Further analyses provided a possible explanation for this discrepancy. First, the distribution of voxels predictable by voxelwise models for each symmetric pair manifested little overlap between the symmetric pair (on average, 20.8% of predictable voxels for any of the paired labels). Second, the weight of voxelwise models mapped onto the cortex revealed that the positive/negative and linear/nonlinear coding of each symmetric pair was highly mixed and distributed across the cortex. These results indicate the cortical representation of the symmetric pairs are highly distributed and heterogeneous, providing new insight into the cortical representation of semantically symmetric information. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-090
日本語文理解における視点取得と脳内コネクティビティ-性別ならびに自閉的傾向との関わり
Effective connectivity for perspective-taking in Japanese sentence comprehension and its correlation with autistic tendency.
*時本 真吾(1)、時本 楠緒子(2)
1. 目白大学、2. 尚美学園大学
*Shingo Tokimoto(1), Naoko Tokimoto(2)
1. Mejiro University, 2. Shobi University
Keyword: Perspective-taking, Effective connectivity, electroencephalogram, beta suppression
This study discusses the neural connectivity for the perspective-taking in verbal communication by examining the electroencephalogram (EEG) associated with the sentence comprehension in Japanese. We manipulated the perspective-taking in sentence comprehension with two Japanese giving verbs, "ageta" and "kureta," which can function as subsidiary benefactive verbs to constitute various compound verbs. "Ageta" and "kureta"as subsidiary verbs require the perspective from the subject for the former as in (3) and that from the dative object for the latter as in (4) respectively.
(3) {a. Watashi/b. Taro}-ga Hanako-ni golufu-o oshiete-ageta.
‘I/Taro gave a lesson in golf to Hanako.’
(4) Taro-ga {a. watashi/b. Hanako-ni} golufu-o oshiete-kureta.
‘Taro gave a lesson in golf to me/Hanako.’
When "watashi" (I, the speaker) is the subject of a sentence with "-ageta" as in (3a) or it is the dative object of a sentence with "-kureta" as in (4a), the sentences are produced from the perspective of the speaker. On the other hand, when "watashi" is replaced by the third person pronoun ("Taro" as in (3b) or "Hanako" as in (4b)), the perspective is assumed to be shifted to the third persons. When we assume that the lister shares the perspective of a speaker, the lister will shift the perspective from the speaker to the third persons for (3b,4b). We recorded the EEG associated with the auditory presentation of the sentences in (3) and (4), and we observed a significant beta suppression for (3b,4b) against (3a,4a) in the time window of 200 to 600 ms in the right central region on the scalp after the onset of "ageta" and "kureta." The sources of the beta suppression were localized to the left insula and the right hippocampus. We calculated the effective connectivity between the two sources by the partial directed coherences and examined the correlations between the coherences and the subscores of The Autism-Spectrum Quotient (AQ), the ages, and the genders of the participants. We found a significant effective connectivity from the left insula to the right hippocampus in the beta band in the time window of 900 to 1000 ms and the connectivity was significantly correlated with the imagination subscale of AQ and the gender of the participants. This result suggests that the perspective-taking in verbal communication is partially realized by the connectivity between brain regions and the degree of the connectivity is graded according to the autistic tendency and the gender of speakers. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-091
意味を持たない言語要素から意味を持つ言語要素への構造化に関わる神経基盤
Neural basis of structuring sublexical constituents to a lexical constituent during comprehension of sequentially presented letterstrings: an fMRI study
*加世堂 竜太郎(1,2)、渡辺 卓爾(1,2)、飯島 淳彦(1,3,4)、中原 潔(5)、足立 雄哉(2)、保前 文高(6)、橋本 龍一郎(7)、福多 真史(8)、白水 洋史(8)、長谷川 功(2)
1. 新潟大学大学院自然科学研究科電気情報工学専攻、2. 新潟大学大学院医歯学総合研究科神経生理学分野、3. 新潟大学医学部保健学科、4. 新潟大学工学部工学科、5. 高知工科大学脳コミュニケーション研究センター、6. 東京都立大学人文社会学部言語科学教室、7. 東京都立大学大学院人文科学研究科言語科学教室、8. 国立病院機構西新潟中央病院機能脳神経外科
*Ryutaro Kasedo(1,2), Takuji Watanabe(1,2), Atsuhiko Iijima(1,3,4), Kiyoshi Nakahara(5), Yusuke Adachi(2), Fumitaka Homae(6), Ryu-ichiro Hashimoto(7), Masafumi Fukuda(8), Hiroshi Shirozu(8), Isao Hasegawa(2)
1. Graduate School Science & Technology, Niigata University, Niigata, Japan, 2. Department of Physiology, School of Medicine, Niigata University Niigata, Japan, 3. School of Health Sciences, Faculty of Medicine, Niigata University, Niigata, Japan, 4. Interdisciplinary Program of Biomedical Engineering, Assistive Technology, and Art and Sports Sciences, Faculty of Engineering, Niigata University, Niigata, Japan, 5. Research Center for Brain Communication, Kochi University of Technology, Kochi, Japan, 6. Department of Language Sciences, Tokyo Metropolitan University, Tokyo, Japan, 7. Department of Language Sciences, Graduate School of Humanities, Tokyo Metropolitan University, 8. Department of Neurosurgery and Epilepsy Center, Nishi-Niigata Chuo National Hospital, Niigata, Japan
Keyword: Linguistic merge process, Sublexical unit, Lexical unit, fMRI
Comprehension of a written sentence requires dual-step ‘merge’ processes across different levels of linguistic hierarchy. The first level merge process is to combine sublexical units (kana letters or alphabets) into the minimal lexical unit (Bunsetsu or word), and the second level merge process is to struct the lexical units into a phrase or higher-order linguistic constituent. In this research, we focus on the 1st-level linguistic merge process in which streams of sublexical constituents are initially combined into a lexical unit. Our previous study showed that during the 2nd-level linguistic merge the areas in the left language network, including left inferior frontal gyrus (IFG), temporal pole (TP) and superior temporal sulcus (STS), were activated as the number of to-be-merged lexical units increased. Other previous studies also showed activations of the left IFG in the 2nd-level merge. However, neural mechanisms of the 1st-level merge process remain largely unknown because the process is done almost automatically after a lexical unit presentation in conventional linguistic tasks. To address this issue, we conducted functional magnetic resonance imaging while 42 normal participants performed the self-paced sequential letterstring reading task we developed. The task enables to control the timing of the 1st-level merge processes in the temporal axis (Kasedo et al 2021). We have done the multiple regression analysis without orthogonalization by using statistical parametric mapping (SPM12, https://www.fil.ion.ucl.ac.uk/spm/). The areas where activation varied depending on the number of merged sublexical units and timing of merge were searched for the 1st-level merge. For the 1st-level merge, the activation areas which were modulated parametrically with the number of to-be-merged sublexical units were located in the left anterior middle temporal gyrus, posterior cingulate gyrus and the opercular part of left IFG (IFGoper), while those modulated with the number of merged sublexical units were located in the bilateral temporal lobes around the temporal pole and the superior temporal sulcus. Furthermore, the left IFGoper adjacent to the precentral sulcus deactivated transiently as the timing that sublexical units were combined into a lexical unit. These results suggest dynamic interplay between excitatory and inhibitory neural circuits underlying the 1st-level linguistic merge. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-092
語の形態的複雑さによる事象関連電位N400の変調: 日本語派生名詞のERP研究
Modulation of the N400 by morphological complexity of words: An ERP study of Japanese derived nouns
*中島 潤(1)、太田 真理(2)
1. 九州大学大学院人文科学府、2. 九州大学人文科学研究院
*Jun Nakajima(1), Shinri Ohta(2)
1. Dept. Ling., Grad. Sch. Hum., Kyushu Univ., 2. Dept. Ling. Fac. Hum., Kyushu Univ.
Keyword: N400, word recognition, language processing, ERP
Previous neuroimaging studies have reported that morphologically complex words elicited cortical activations around 300-500 ms after the word onset (N400/M350) in the left temporal lobe. The Japanese language has two types of derived nouns, which are different in their morphological complexity (e.g., simple stem: [[samu]-sa], coldness; complex stem: [[bu-[atsu]]-sa], thickness). In the present EEG experiment, we examined how the morphological complexity of derived nouns (i.e., number of morphemes) modulates the N400.
We recruited 20 right-handed native speakers of Japanese (7 males, 23.4 ± 2.3 yrs.). We used 52 stimuli for the derived noun with simple stem (e.g., samu-sa) and 26 stimuli for the derived noun with complex stem (buatsu-sa), as well as 78 nonwords (*samusi-sa) (total 156 stimuli). The participants performed visual lexical decision tasks. We used a 64-electrode EEG system (Nihon-Kohden) to acquire EEG data. Our primary target was the N400, which is typically observed in the bilateral parieto-occipital and temporal regions. We selected four regions of interest (left/right temporal, central, and parieto-occipital ROIs). The analysis time window was restricted to 300-500 ms after word onset.
Behavioral data showed that the mean accuracies of the lexical decision task of the three conditions were > 85%. We examined whether the number of morphemes modulated the N400 using a linear mixed-effect model and a cluster permutation test (lme4 and permutes packages on R). We found that the earlier subcomponent of the N400 (319-344 ms) in the left temporal ROI showed a significant positive correlation with the morphological complexity (corrected p < 0.05), while the latter subcomponent of the N400 (450-466 ms) in the four ROIs showed a negative correlation (corrected p < 0.05). These results indicated that the earlier subcomponent reflected the decreasing processing loads of lexical access due to the higher frequency of morphemes. In contrast, the negative correlation between the amplitude of the latter subcomponent and morphological complexity suggested higher processing loads of recombining morphemes. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-093
Tickle Response in Rat Posterior Insular Cortex
*Vsevolods Girsovics(1), Shimpei Ishiyama(1)
1. University Mecidal Center of the Johannes Gutenberg-University Mainz
Keyword: Insula, play behavior, ultrasonic vocalizations, in-vivo electrophysiology
Social play is a readily recognizable feature of human development. Nonhuman mammals also engage in social play, which have been shown to shape their emotional and cognitive development. It is well studied in adolescent rats via heterospecific play (human tickles a rat), mainly via recording of 50 kHz ultrasonic vocalizations (USV), a characteristic feature of this phenomenon. After behavioral confirmation of social play in rats, Ishiyama and Brecht (2016) revealed the first neural correlates of ticklishness in the somatosensory cortex of rats. This sensory characterization of social play led us to study the emotional processing of this pathway in the posterior insular cortex (pIC). Insula is regarded as a hub, integrating sensory, emotional and cognitive information, making extrinsic and intrinsic stimuli become salient. In this system, the pIC is thought to process sensory information, and is therefore the putative downstream region for the processing of ticklish sensation. Using in-vivo electrophysiology, heterospecific play and recording of USV, we could show tickling-evoked neuronal response in the far posterior pIC, yet gentle touch also evoked neuronal response in the pIC. Moreover, neuronal response could be also observed during bipedal jumps, which is another characteristic of social play in adolescent rats, typically occurring after tickling interactions. To further specify the area processing social play, acute somatosensory mapping was performed in the pIC of adolescent rats. While gentle stroke did not show any response, palpating touch of the dorsal trunk, resembling tickling interaction, led to a strong response in the far posterior pIC. Though these results have to be confirmed by neuronal tracing and physiological manipulation experiments, they indicate that the pIC may indeed be the downstream area of the somatosensory response to tickling interactions in the pathway processing social play in adolescent rats. The discrepancy in gentle touch response in the pIC between mapping and chronic experiments may have occurred due to anticipation of being tickled in the chronic experiment. Anticipation has been shown to be processed in the insula as well, and this assumption is strengthened by the observation of USV during and jumps after gentle touch, both of which typically do not occur in this condition. In conclusion, our preliminary results suggest involvement of the pIC in the processing of social interactions in rats beyond somatosensation. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-094
マウスの前頭前皮質は長期の社会的認知記憶に必須である
The prefrontal cortex is necessary for long-term social recognition memory in mice
*坂本 敏郎(1)、八島 成維(1)
1. 京都橘大学
*Toshiro Sakamoto(1), Joi Yashima(1)
1. Kyoto Tachibana University
Keyword: SOCIAL RECOGNITION MEMORY, PRINFRONTAL CORTEX, MOUSE, LONG-TERM MEMORY
The prefrontal cortex (PFC) is critical for social cognitive function in rodents; however, its role in social recognition memory is not fully understood. Here, we therefore examined its role in long-term and short-term social recognition memory in mice. We lesioned the PFC in C57BL/6J male mice (age: 8 weeks) with ibotenic acid. Lesioned mice (n = 21) and sham-lesioned control mice (n = 21) then performed the social recognition test (SRT), light and dark test (LDT), and open field test (OFT). The SRT comprised three 5-min trials on 3 consecutive days (10 min between trials). In each trial, a stimulus mouse in a transparent cylinder was presented to the test mouse and the duration of social investigation (SI) was recorded, as indexed by time spent sniffing toward the mouse in the cylinder. An adult (age: 8 weeks) or juvenile (age: 3 weeks) male mouse was used as the stimulus mouse on each day for the lesion and sham groups. Thus, SI duration was compared across four conditions (lesion-juvenile, lesion-adult, sham-juvenile, sham-adult). In the OFT and LDT, mice freely explored either the open field or the light-dark box for 10 min.On the SRT, both PFC-lesioned mice and sham-control mice spent more time investigating the juvenile mouse than the adult mouse. Over time, both within each day and across days, sham mice spent less time investigating the stimulus mice. In contrast, while SI duration in PFC-lesioned mice decreased across the three trials within each day, it did not decrease across the 3 days. Thus, while mice normally develop both short-term and long-term habituation to new conspecifics, PFC-lesioned mice only exhibited normal short-term habituation; they did not develop long-term habituation, indicating that they did not remember the mice they had been introduced to on previous days. PFC lesions did not affect behavior in the OFT or LTD. These results suggest that the PFC plays an important role in long-term, but not short-term, social recognition memory. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-095
高濃度テストステロンはNeurexinとNeuroliginとの結合阻害を介して社会性行動異常を呈する
Highly concentrative testosterone impaired social behavior by interrupting Neurexin and Neuroligin binding
*柳下-姜 楠(1)、丸山 敬(1)
1. 埼玉医科大学 薬理学
*Nan Yagishita-Kyo(1), Kei Maruyama(1)
1. Dept. Pharmacol, Saitama Med Univ, Saitama, Japan
Keyword: Autism Spectrum Disorder, Testosterone, Neurexin, Neuroligin
Autism spectrum disorder (ASD) is characterized by social communication deficits. Modern research has indicated that inherited defects of synapse formation or maintenance cause familial ASD. Especially, synaptic adhesion molecules, such as Neurexin and Neuroligin, have gotten a lot of attention as responsible genes of ASD. More importantly, Neurexin binds to Neuroligin at synaptic cleft, and this intercellular binding is also related to the manifestation of social behavior. We have been investigating whether the change of Neurexin-Neuroligin binding intensity cause sporadic ASD.
Previously, we have found testosterone as a molecule that affects Neurexin-Neuroligin binding in vitro. Testosterone, one of the main male hormones, directly binds to Neurexin and interrupts the cell-to-cell binding of Neurexin and Neuroligin. Interestingly, testosterone is another key molecule of higher incidence of ASD in male. There is a remarkable sex difference in ASD, and it is thought to be related to high level of fetal testosterone.
Therefore, we hypothesized that high level testosterone interrupts Neurexin-Neuroligin binding, leading to the synapse formation and social behavior deficits. We injected testosterone to pregnant mice and assayed their neonate brain. In our assay, Neurexin-Neuroligin binding was decreased by testosterone injection. We also investigated the social preference behavior. Male mice showed social impairment in juvenile stage, whereas female mice showed social impairment only after in adulthood by testosterone injection. On the other hand, the performances of novel object recognition task and Y-maze task were not changed. Our results suggest the missing link of sporadic ASD-causing mechanisms by Neurexin, Neuroligin and testosterone. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-096
マウスの前部帯状皮質と前辺縁皮質の社会的動機づけおよび短期の社会的記憶における機能的差異
Functional differences in social motivation and short-term social recognition memory between the anterior cingulate and prelimbic cortices in mice
*八島 成維(1)、上北 朋子(1)、坂本 敏郎(1)
1. 京都橘大学健康科学研究科
*Joi Yashima(1), Tomoko Uekita(1), Toshiro Sakamoto(1)
1. Grad Sch Health Sciences, Kyoto Tachibana Univ, Kyoto, Japan
Keyword: social recognition memory, social motivation, prelimbic cortex, anterior cingulate cortex
The prefrontal cortex (PFC) plays important roles in mouse social cognition. However, exactly which subregions of the PFC are involved in social memory and social motivation remain unknown. Here, we examined the role of two regions of the PFC—the anterior cingulate cortex (ACC) and the prelimbic cortex (PL)—in social recognition memory and social motivation toward novel conspecifics. We lesioned the ACC or the PL of C57BL/6J male mice (age: 7 weeks) with ibotenic acid. After recovery, the lesioned mice along with sham-lesioned control mice performed the social recognition test (SRT), social novelty test (SNT). The SRT comprised five trials (5 min/trial with a 5-min intertrial interval); a transparent cylinder was used to present the same stimulus mouse to a test mouse in the first four trials, and a novel stimulus mouse (same age) in the last trial. The SNT followed the same procedures as the SRT, except different stimulus mice were presented in each of its four trials. We recorded the duration of test mouse social investigation (SI), indexed by sniffing toward the mouse in the cylinder. On the SRT, habituation and dishabituation were normal in the ACC-lesioned mice (comparable with the ACC-sham and PL-sham control mice). In contrast, while habituation was normal in the PL-lesioned mice, they did not exhibit dishabituation. In the SNT, SI duration (social behavior) was comparable between the ACC-lesioned mice and ACC-sham mice. However, it was significantly shorter in the PL-lesioned mice than in PL-sham mice. These results indicate that the PL but not the ACC is involved in both short-term social memory and social motivation toward novel mice. Thus, the PL might act to facilitate investigation toward novel conspecifics and to discriminate among conspecifics. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-097
A thalamo-preoptic pathway promoting social touch
*Keller David(1,2)、Lang Tamas(1)、Cservenak Melinda(2)、Puska Gina(2)、Barna Janos(1)、Dobolyi Arpad(1,2)
*David Keller(1,2), Tamas Lang(1), Melinda Cservenak(2), Gina Puska(2), Janos Barna(1), Arpad Dobolyi(1,2)
1. Dep of Anat, Semmelweis Uni, Budapest, Hungary, 2. Dep Phys and Neurobiol, Eötvös Loránd Research Network and Eötvös Loránd Uni, Budapest, Hungary
Keyword: social behavior, posterior thalamus, preoptic area of hypothalamus, chemogenetics
We previously identified the posterior intralaminar thalamic nucleus (PIL) as a relay station of socially relevant sensory information innervating and activating oxytocin-secreting neurons upon social encounter. Here, we addressed to characterize the exact role of the PIL neurons and their projections to the preoptic area of the hypothalamus in the control of the social behavior. First, we determined the effect of chemogenetic stimulation of PIL neurons on social interactions between familiar adult female rats using the DREADD technique. The brain activation patterns were determined following direct social interaction, and also with the exclusion of physical interaction using the c-Fos technique. The projections of PIL neurons were analyzed using anterograde tract-tracing. The selective chemogenetic stimulation of the preoptic area-projecting PIL neurons was performed using double viral injections and also by using intracerebral cannula for CNO administration directly into the preoptic area. PIL projects to several socially implicated brain regions, such as the medial amygdala, the medial preoptic area, the paraventricular and dorsomedial hypothalamic nuclei and the infralimbic cortex. Chemogenetic stimulation of the PIL resulted in the activation of previously anatomically identified target areas and also increased the duration of direct interactions during social behavior. Direct contact during social interaction caused the largest increase in the activity in the medial preoptic area. Specific chemogenetic stimulation of the PIL-preoptic pathway led to elevated direct social contact. The results suggest that posterior thalamic PIL neurons convey socially relevant information to a variety of different forebrain centers, among which the preoptic area is involved in the processing of physical contact. Thus, we identified an important novel component of the social brain network, which may increase the motivation for positive direct interactions. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-098
ニューロリジン３による行動調節の分子基盤
Distinct roles of canonical and non-canonical neuroligin 3 pathways in behavioral regulation
*今井 彩子(1)、和泉 宏謙(1)、腰高 由美恵(2)、高雄 啓三(3,4)、森 寿(1,4)、吉田 知之(1,4)
1. 富山大学医学部分子神経科学講座、2. 富山大学生命科学先端研究センター、3. 富山大学医学部行動生理学講座、4. 富山大学アイドリング脳科学研究センター
*Ayako Imai(1), Hironori Izumi(1), Yumie Koshidaka(2), Keizo Takao(3,4), Hisashi Mori(1,4), Tomoyuki Yoshida(1,4)
1. Department of Molecular Neuroscience, Faculty of Med, Univ of Toyama, Japan, 2. Life Science Research Center, Univ of Toyama, Japan, 3. Department of Behavioral Physiology, Faculty of Med, Univ of Toyama, Japan, 4. Research Center for Idling Brain Science, University of Toyama, Japan
Keyword: SYNAPSE ORGANIZER, SOCIABILITY
Neuroligin (NLGN) 3 is a well-characterized postsynaptic cell adhesion protein that organizes synapse formation through interaction with presynaptic neurexins (NRXNs) and dysregulated NLGN3 signaling is implicated in autism spectrum disorders. We recently identified non-canonical interaction between NLGN3 and presynaptic protein tyrosine phosphatase δ (PTPδ), which competes with the canonical NLGN3-NRXN interaction. The identification of the non-canonical NLGN3-PTPδ interaction prompted us to examine its physiological and pathological roles in behavioral regulation. We thus generated two knock-in mutant mice with Nlgn3 gene mutations that selectively impair either NLGN3-NRXN or NLGN3-PTPδ interaction, and subjected these mutants to behavioral test battery. Nlgn3hse mutants that lack the canonical NLGN3-NRXN pathway exhibited more preference to a stranger mouse than littermate control mice in the three-chamber sociability test. In contrast, Nlgn3mf mutants impairing the non-canonical NLGN3-PTPδ pathway showed no obvious social preference to the stranger mouse in the three-chamber sociability test. Nlgn3mf mutants, furthermore, showed enhanced motor learning in the accelerated rotarod test and impairment in remote spatial reference memory in the Barnes maze test. On the other hand, the Nlgn3hse mice demonstrated no significant differences in the rotarod test and the Barnes maze test. Nlgn3hse mutants however showed decreased freezing rate in the contextual fear conditioning. These differential social and learning/memory phenotypes between Nlgn3hse and Nlgn3mf mutants suggest that the canonical and non-canonical NLGN3 pathways play distinct roles in behavioral regulation. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-099
Behavioral alterations by nano-plastics administration in mice.
*Na-Hyun Kim(1), Jae-Won Jung(1), Yukiori Goto(2), Young-A Lee(1)
1. Dept Food Sci & Nutr, Daegu Catholic Univ, Gyeongsan, South Korea, 2. Primate Res Inst, Kyoto Univ, Aichi, Japan
Keyword: Nano-plastics, Social behavior, Dopamine, Serotonin
In our modern society, environmental pollutants, such as nano- and micro-palstics in domestic wastes are thought to affect human health. It has been reported that nano-plastics (NPX) are accumulated in the human body through the food chain ecosystem. Accumulating evidence suggests that NPX may cause behavioral alterations in some fish and rodents. However, it remains largely unclear how NPX causes neuronal alterations and brain dysfunction, especially given that environmental pollutants other than NPX, such as bisphenol and phthalate, are also suggested to induce cognitive dysfunction. In this study, we investigated how excessive intake of NPX affected neurodevelopment in mice. NPX was orally administered once per a day for 14 days at the dose of 6.066*10^7 or 6.066*10^12 particles/kg in different developmental periods. Mice were divided into 6 groups by the treatment periods, either from gestational day 7 to 12 (denoted as GTD7), from GTD13 to the birth (GTD13), from postnatal day (PND) 21 to PND35 (PND21), from PND38 to PND56 (PND38), or from PND56 to PND70 (PND56). Control mice with vehicle (VEH) treatment received distilled water orally in the corresponding periods. We investigated locomotion and social behavior of these mice 14 days after NPX administration. In the locomotor test, mice with GTD7 treatment at the dose of NPX 6.066*10^12 selectively exhibited decreased locomotor distance. We are currently analyzing and will present the effects of NPX treatments on social behavior and the dopamine and serotonin systems. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-100
外側視床下部から背側縫線核に投射する神経細胞の活性化が、オスマウスの攻撃行動に与える影響。
Effects of excitation of the lateral hypothalamic neurons projecting to the dorsal raphe nucleus on aggressive behavior in male mice.
*三井 鴻志郎(1)、高橋 阿貴(2)
1. 筑波大学 人間総合科学研究群 ニューロサイエンス学位プログラム、2. 筑波大学 人間系
*Koshiro Mitsui(1), Aki Takahashi(2)
1. Grad. Sch. Comprehensive Human Science, University of Tsukuba, Ibaraki, Japan, 2. Faculty of Human Science, University of Tsukuba, Ibaraki, Japan
Keyword: Aggressive behavior, Mice, Predatory aggression, Lateral hypothalamus
Both the lateral hypothalamus (LH) and the dorsal raphe nucleus (DRN) has been implicated in the neural bases of intraspecific aggression and predatory aggression, and these two brain regions densely connect each other by reciprocal projections. However, the function of LH neurons that project to the DRN (LH-DRN projection) in these aggressive behaviors has not been studied. In this study, we used optogenetics to examine the possible involvement of LH-DRN projection on these aggressive behaviors. The channelrhodopsin-2 (ChR2) expressing AAV was injected into the bilateral LH of male mice, and optic fiber was inserted in the DRN to stimulate the projection terminals. Five weeks after the AAV injection, intraspecific aggression, predatory aggression as well as feeding behavior were examined with and without optical stimulation. We introduced either a male or female intruder in the resident intruder test to examine inter-male (5 min test) and toward-female aggression (10 min test). For predatory aggression, we observed bite behavior toward crickets or artificial prey for 10 minutes. In addition, feeding behavior toward a standard food pellet was examined for 10 minutes in mice fed ad libitum. Optical stimulation was delivered using laser (10 ms blue light (473nm) pulses at 20 Hz), and two different light intensities were examined (around 1.0 mW and 3.0 mW) to minimize the leaking of light into the neighboring region of the DRN (i.e. periaqueductal gray). Our results showed that optogenetic activation of the LH-DRN projection using 3.0 mW output increased the number of bites in any form of aggression, including inter-male, toward female, and predatory aggression (both toward crickets and artificial prey), but did not affect other aggressive behaviors such as sideways threats and tail rattles. In addition, LH-DRN activation induced feeding behavior. The same effects were observed even with 1.0 mW light intensity. After all behavioral experiments are completed, c-Fos expression in the DRN was examined after 1 min light stimulation by immunohistochemistry. We observed that the light stimulation increased c-Fos expression in the DRN. In conclusion, these results indicated that the LH-DRN projection activates DRN neurons and induces bite behavior toward any kind of stimulus in male mice. In the further research, we are currently investigating the effects of DREADD inhibition of LH-DRN circuits on these aggressive behaviors and feeding behavior. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-101
マウスの自発活動量でみられる社会的促進に対する5HT神経系の関与
Social facilitation is regulated by 5HTergic system.
*古川 敏基(1,2)、藤原 智徳(3)
1. 埼玉医科大学国際医療センター、2. 埼玉医科大学大学院医学研究科、3. 埼玉医科大学保健医療学部
*Toshiki L Furukawa(1,2), Tomonori Fujiwara(3)
1. Saitama Med Univ International Medical Center, Saitama, Japan, 2. Grad Sch Med, Saitama Med Univ, Saitama, Japan, 3. Faculty of Health & Medical Care, Saitama Med Univ, Saitama, Japan
Keyword: Social facilitation , 5HT, Syntaxin, Locomotor activity
Social environment is known to affect to cognitive and behavioral properties in most of animals. For example, the presence of affiliative conspecific reduces stress response(social buffering) and improved an individual’s performance (social facilitation: SF). These phenomenon are closely related to social recognition. Human patients with neuropsychological disorder such as autism spectrum disorders (ASD) have deficit of social behavior including difficulty with social communication and impairment of SF. It is thought that a part of these abnormalities are possibly underlay impairment of social recognition. Recent studies demonstrated that synaptic dysfunction related to ASD. HPC-1/syntaxin1A (STX1A) is known to regulate synaptic transmitter release. It was reported that hemizygous deletion of STX1A gene were observed in patients with Williams syndrome. And, it was also found that a part of ASD patients were haploid for the STX1A gene. Previously, we reported that STX1A gene knockout mice (STX1A KO) showed neuropsychological abnormalities including unusual social behavioral profiles. Interestingly, some of these behavioral alternations in STX1A KO was ameliorated by monoaminergic drugs such as SSRI.In order to study regulation of social behavior, we focused on SF using model mice. In this study, we analyzed wheel running in their home cage (locomotor activity) with or without observer mouse. In WT mice, the locomotor activity in the presence of observer mouse was elevated compared with the absence of observer mouse. This phenomenon is thought as SF. In STX1A KO, the basal locomotor activity was not different, but the elevation of locomotor activity was suppressed compared with WT. These observations indicated the reduction of the SF in STX1A KO. We also analyzed the effect of social hierarchy to the SF. In WT, the properties of SF altered in the difference of social rank which determined tube dominance test. Interestingly, 5HT release in these micewere changed by the difference of social rank. We will discuss that SF and regulation of SF by 5HTergic system. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-102
1人称と3人称の私を認識する脳
The salience network is activated during self-awareness from both the first- and third-person perspectives
*朝蔭 晶子(1)、中野 珠実(1)
1. 大阪大学大学院生命機能研究科
*Shoko Asakage(1), Tamami Nakano(1)
1. Grad Sch. Frontier Bioscience, Osaka University, Osaka, Japan
Keyword: self-awareness, first/third-person perspective, precuneus, salience network
Self-awareness can be divided into two aspects. In one, an individual perceives themself from their own viewpoint (first-person perspective), and in the other, they are perceived from the viewpoint of another person (third-person perspective). However, whether the self-awareness associated with these two perspectives has a common or separate neural basis remains unclear. To address this, we used functional magnetic resonance imaging to examine brain activity while twenty four participants viewed pre-taped video clips of themselves and others engaged in meal preparation taken from first- and third-person perspectives. We found that, compared with the third-person behavioral videos, the first-person behavioral videos of the participants and others induced greater activation in the premotor area, post-central area, intraparietal region, and cerebellum. In contrast, the third-person behavioral videos induced greater activation in the default mode network compared with the first-person videos. Regardless of the perspective, the videos of the participants induced greater activation in the anterior insular, dorsal anterior cingulate cortex, and supramarginal gyrus, all of which composes the salience network, than the videos of others. On the other hand, the videos of others induced greater activation in the precuneus and lingual gyrus than the videos of the participants. The precuneus showed the greatest activation to the third-person videos of others, while the lingual gyrus showed the greatest activation to the first-person videos of others. These results suggest that the salience network is commonly involved in self-awareness from both perspectives, even though the brain regions involved in action observation for the two perspectives are distinct. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-103
USVCAM：マウス超音波発声を計測する超音波カメラ
USVCAM: acoustic camera system for measuring ultrasound communication in mice
*菅野 康太(1)、松本 惇平(2,3)、加藤 雅裕 (4,5)、西丸 広史(2,3)、瀬戸川 剛(2,3)、Choijiljav Chinzorig(2)、柴田 智広(6)、西条 寿夫(2,3)
1. 鹿児島大学法文学部、2. 富山大学医学系、3. 富山大学アイドリング脳科学研究センター、4. 加藤建築環境研究所、5. 関東学院大学建築・環境学部、6. 九州工業大学生命体工学研究科
*Kouta Kanno(1), Jumpei Matsumoto(2,3), Masahiro Kato(4,5), Hiroshi Nishimaru(2,3), Tsuyoshi Setogawa(2,3), Choijiljav Chinzorig(2), Tomohiro Shibata(6), Hisao Nishijo(2,3)
1. Faculty of Law, Economics and Humanities, Kagoshima University, Kagoshima, Japan, 2. Faculty of Med, University of Toyama, Toyama, Japan, 3. Res Center for Idling Brain Sci, University of Toyama, Toyama, Japan, 4. Katou Acoustics Consultant Office, Yokohama, Japan, 5. Osawa Memorial Institute of Architectural Environmental Engineering, Kanto Gakuin University, Yokohama, Japan, 6. Grad Sch of Life Sci and Systems Engineering, Kyushu Institute of Technology, Kitakyushu, Japan
Keyword: ultrasonic vocalizations, sound localization, social behavior, mice
In mice, ultrasonic vocalizations (USVs) are used for communication, and they can be widely observed in both wild and laboratory strains. Adult male mice emit ultrasounds in the presence of adult females or their urine; these are known as courtship vocalizations or courtship songs (male-female). Females emit USVs to females (female-female), whereas they rarely emit to males. In many cases, ultrasound recordings are conducted using the resident-intruder paradigm. Besides, it is reported that the primary source of vocalizations is resident males in the male-female context and resident females in the female-female context, in the C57BL/6 strain. However, here, we demonstrate the high vocal contribution of both resident and intruder individuals in the ICR strain. We developed a novel sound source localization system combined with markerless tracking, named USVCAM. Our system can localize USVs in various experimental conditions, such as the resident-intruder paradigm, which has been difficult in previous systems and thus can widely provide new opportunities to analyze social behaviors in mice. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-104
シナプス形成抑制因子ＭＤＧＡ１/２の欠失は対蹠的な興奮/抑制バランス偏移と行動異常を引き起こすが、成年期の薬剤投与により回復できる
Reduction of MDGA1/2 induces opposed impairments in E/I balance to cause behavioral deficits, those can be rescued by administration of adequate drugs in their adulthood.
*山本 融(1)、尾嶋 大喜(1)、多田 篤史(1)、窪田 剛志(2)、髙橋 弘雄(1)、冨永 貴志(2)、岸本 泰司(3)
1. 香川大学医学部、2. 徳島文理大学香川薬学部、3. 帝京大学薬学部
*Tohru Yamamoto(1), Daiki Ojima(1), Atsushi Tada(1), Takashi Kubota(2), Hiroo Takahashi(1), Takashi Tominaga(2), Yasushi Kishimoto(3)
1. Fac Med, Kagawa Univ, Kagawa, Japan, 2. Kagawa Sch Pharm Sci, Tokushima Bunri Univ, Kagawa, Japan, 3. Fac Pharm Sci, Teikyo Univ, Tokyo, Japan
Keyword: E/I BALANCE, SOCIAL BEHAVIOR, MDGA, ASD
The molecular basis of our cognition and behavior resides in neuronal networks connected with excitatory and inhibitory synapses. Formation of these synapses requires highly coordinated orchestration of trans-synaptic communication between pre- and post- synaptic molecules, and the resultant proper excitatory/inhibitory balance (E/I balance) is crucial for brain function. The interaction between presynaptic Neurexin (NRX) and postsynaptic Neuroligin (NLGN) plays a central role in synapse differentiation, maturation, and activity-dependent modification, and their genetic alterations are linked to psychiatric disorders such as schizophrenia and ASD. MDGAs are GPI-anchored IgSF molecules that consist of two closely related family members: MDGA1 and MDGA2. MDGA1/2 directly associate with NLGNs to interfere their bindings to NRXs for preventing inappropriately excess synapse formation; decreasing MDGA1 protein induces excess inhibitory synapse formation and decreasing MDGA2 protein induces excess excitatory synapse formation. As a result, MDGA1/2 deficient mice exhibit reduced LTP in hippocampus and suffer learning and memory deficit. MDGA1 deficient mice also exhibit sensory gating abnormality frequently observed in schizophrenia, and MDGA2 deficient mice exhibit deficits in social behavior observed in ASD. Interestingly, MDGA1 and MDGA2 deficient mice exhibited contrasting abnormalities in some social behaviors, suggesting that such behavioral abnormalities can be normalized by adequate drugs that neutralize the E/I imbalance. In fact, we found that acute administration of such drugs significantly improved behavioral abnormalities observed in MDGA1 and MDGA2 deficient mice even in their adulthood. Our findings underscore the relevance of E/I balance in higher-ordered brain function, some of which impairment could be attenuated by adequate reagents modulating E/I input even in adulthood. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-105
内側視索前野へ投射する扁桃体海馬野ニューロンは養育行動にて相反する亜集団を有する
The positive and negative neural subpopulations in paternal behavior of the amygdalohippocampal area neurons projecting to the medial preoptic area
*佐藤 圭一郎(1)、奥野 浩行(2)、尾藤 晴彦(3)、南 雅文(1)、天野 大樹(1)
1. 北海道大学 大学院薬学研究院 薬理学研究室、2. 鹿児島大学 医歯学総合研究科 先進治療科学専攻 生体機能制御学講座、3. 東京大学 大学院医学系研究科 脳神経医学専攻 神経生化学教室
*Keiichiro Sato(1), Hiroyuki Okuno(2), Haruhiko Bito(3), Masabumi Minami(1), Taiju Amano(1)
1. Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Hokkaido University, 2. Department of Biochemistry and Molecular Biology, Graduate School of Medical and Dental Sciences, Kagoshima University, 3. Department of Neurochemistry, Graduate School of Medicine, The University of Tokyo
Keyword: amygdalohippocampal area, social behavior, E-SARE, scRNA-seq
We previously reported that activation of the amygdalohippocampal area (AHi) neurons projecting to the medial preoptic area (MPOA), a key region of parenting behavior, disrupted parenting and promoted pup-directed aggression behavior (Sato et al., 2020). However, c-Fos immunostaining analysis revealed that MPOA-projecting AHi neurons were activated by both parenting and aggression toward pups. We therefore hypothesized that MPOA-projecting AHi neurons consist of a parenting subpopulation and an attack subpopulation, and that activation of both subpopulations enhances aggression rather than parenting.
To assess this possibility, we attempted to specifically label each MPOA-projecting AHi population by projection-specific, activity-dependent expression of Cre recombinase using a retorograde adeno-associated virus (AAV2retro) vector. In order to achieve the high signal-to-noise ratio of activity-dependent Cre expression, we generated the AAV2retro vector containing a drug-controlled destabilized Cre recombinase (DD-Cre)(Sando et al., 2013) under the control of the Arc-derived strong activity-dependent promoter, E-SARE (Kawashima et al., 2013), combined with the TET-ON system (AAV2retro-ESARE-Tet3G-Ins-TRE3G-DD-Cre). We injected this retrograde vector into the MPOA and labeled AHi neurons activated during either parenting or attacking behavior with a red fluorescent protein upon drug administration. We examined the overlap between cells labeled by this strategy and cells expressing c-Fos as the endogenous activity marker, following either parenting or aggression. We observed a lower overlap in cells labeled by different behavior than same behavior, suggesting two functionally distinct subpopulations.
Given the functional separation of parenting and attack subpopulations, we next performed scRNA-seq to determine whether the two populations were molecularly distinct. scRNA-seq results were subjected to clustering and DEG analysis, which revealed that 395 genes were found to exhibit higher expression levels in the parenting subpopulation than in the attack subpopulation, and 755 genes showed the opposite pattern. Then, we performed in situ hybridization to visualize mRNA expression of a subset of these genes and found specific expression patterns that were consistent with the scRNA-seq results.
Finally, we investigated electrophysiological properties of parenting and attack subpopulations by whole-cell patch-clamp recording. As the results, input resistance and firing rates of neurons in the parenting population were lower than in the attack population.
In conclusion, our study suggested that the presence of distinct subpopulations of MPOA-projecting AHi neurons functionally, molecularly, and physiologically. We are currently exploring how each neural population is regulated to modulate pup-directed behavior. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-106
背側縫線核のメラノコルチン3/4受容体を介したマウスの養育行動の発現調節機構
Regulation of maternal care by melanocortin 3/4 receptor in the dorsal raphe nucleus in lactating female mice
*室井 喜景(1)、牧口 広人(1)、石井 利明(1)
1. 帯広畜産大学 獣医学研究部門
*Yoshikage Muroi(1), Hiroto Makiguchi(1), Toshiaki Ishii(1)
1. Obihiro University of Agriculture and Veterinary Medicine
Keyword: melanocortin receptor, dorsal raphe nucleus, maternal care
Maternal care is indispensable for survival of neonates in mammals. Lactating females consume a large amount of energy for nurturing their pups by lactation. Management of energy expenditure through lactation is important for survival of lactating females and their pups. An appropriate behavior of females, namely lactating behavior, is necessary for giving pups milk. Food intake may affect lactating behavior. We previously reported that the orexigenic neuropeptide neuropeptide Y in the dorsal raphe nucleus (DRN) regulated maternal care, depending on food intakes of lactating females. In the present study, we investigated the neuronal mechanism for regulating maternal care by melanocortin 3 and 4 receptors (MC 3/4R), which were regulated by the anorexigenic neuropeptide alpha-melanocyte-stimulating hormone (α-MSH) and the orexigenic neuropeptide agouti-related peptide (AgRP) in an opposing manner. Neuronal processes immunoreactive to adrenocorticotropic hormone (ACTH), which was a precursor of α-MSH, or AgRP, were distributed in the DRN. Furthermore, the pre-synaptic marker synaptophysin was co-localized with ACTH or AgRP in the DRN. We next investigated how the MC3/4R antagonist SHU 9119 affected maternal care. Injection of 100 pmol SHU 9119 into the DRN prevented maternal care in fed dams. Additionally, we examined whether the agonist melanotan II could affect maternal care following fasting for 8 h. Fasting for 8 h abolished maternal care in lactating females. But injection of 100 pmol melanotan II into the DRN partially recovered maternal care. These results indicate that MC3/4R signaling in the DRN regulates maternal care depending on food intake in lactating female mice. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-107
ヒトらしさ・意識・自己他者・心の理論のメカニズムを探究するための、その手前にあるべき概念整理
Conceptual organization for exploring the mechanisms of Humanity, Consciousness, Self-Other, and Theory of Mind.
*阪口 幸駿(1)
1. 同志社大学生命医科学部
*Yukitoshi Sakaguchi(1)
1. Faculty of Life and Medical Sciences, Doshisha University
Keyword: Theory of mind, Human-specific functions, Consciousness, Communication
Today, consciousness, self and others, and the mind are being energetically studied in the brains of rodents, monkeys, and a variety of other animals. The ultimate goal of most of these studies may be to understand "human" consciousness and mind, but can such studies really lead us to the understanding of human uniqueness? In addition, human-specific behaviors and phenomena have been discussed in depth within the disciplines of animal behavior, psychology, and philosophy, but to what extent do the experimenters within the neuroscience field themselves take into account such human-specific behaviors and the cognitive basis of these behaviors in their experiments? In neuroscience, new findings and new experimental methods are rapidly being discovered and developed, and in this respect they can be highly evaluated, but are they really setting goals (understanding human uniqueness) properly, but are the goals (understanding of human uniqueness) that are to be reached by using these methods really being set appropriately? To answer these questions, I will introduce some of the differences between animal behavior and human actions, and introduce the unique behavioral features and cognitive basis that only humans have. In particular, I will explain the establishment of 3-way relational communication through joint attention, the establishment of theory of mind through 3-way relational communication, the establishment of self-consciousness as the second order theory of mind, and the establishment of other uniqueness of humans (language, tool use, action planning, etc.) through self-consciousness. Through this presentation, I would like to explain how the current animal experiments are not contributing to the understanding of human characteristics, and furthermore, I would like to suggest alternative methods and discuss them with the audience. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-108
長期的自発運動はラットにおける恐怖の情動伝染を促進する
Long-term voluntary exercise promotes emotional contagion of fear in rats
*久保田 夏子(1)、山口 小百合(1)、森岡 文(2)、北 一郎(1)
1. 東京都立大学大学院人間健康科学研究科、2. 東京都立大学理学部
*Natsuko Kubota(1), Sayuri Yamaguchi(1), Aya Morioka(2), Ichiro Kita(1)
1. Dept Human Health Sci, Tokyo Met Univ, Tokyo, Japan, 2. Fac Sci, Tokyo Met Univ, Tokyo, Japan
Keyword: empathy, emotional contagion, oxytocin, exercise
Empathy, an innate ability to perceive and be sensitive to the emotional states of others, is contagious and associated with a motivation to care for their wellbeing, including prosocial motivation. The neuropeptide oxytocin (OXT) has been suggested to be involved in empathetic response and emotional contagion. Recently, we found that long-term voluntary exercise could facilitate prosocial behavior via activation of OXT neurons in rats, suggesting that long-term exercise may enhance the sensitivity of OXT neurons. However, whether regular exercise promotes emotional contagion through activation of OXT neurons remains unclear. In the present study, we examined the effect of long-term voluntary exercise on emotional contagion of fear and activation of OXT neurons in rats. We used a behavioral paradigm in which an observer rat witness freezing behavior of a demonstrator received electric foot shocks (FS) 24 hours ago. We measured freezing time of both the observer and demonstrator rats for 20 min. This behavioral experiment was consisted of three conditions: no-demonstrator (CON-1), intact demonstrator (without FS, CON-2), demonstrator with FS (CON-3). In addition, we evaluated activation of OXT neurons in the hypothalamic paraventricular nucleus (PVN) during represented emotional contagion situation for 20 min using immunohistochemistry. The observer rats were pair-housed in the cage with running wheel or without running wheel (Ex-G, nEx-G, respectively) for 4 weeks, while the demonstrators were pair-housed separately with observers. Freezing time of both observers (Ex-G and nEx-G) in CON-3 was significantly increased compared with that in CON-1 and CON-2, as similar as increased freezing time of demonstrators in CON-3. In CON-3, observers in Ex-G showed longer time of freezing behavior than that in nEx-G, while the freezing time in both CON-1 and CON-2 showed no difference between Ex-G and nEx-G. Furthermore, Ex-G showed higher activation of OXT neurons in the PVN during represented situation of CON-3 than nEx-G. These results suggest that long-term voluntary exercise could promote emotional contagion of fear through activation of OXT neurons. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-110
社会的価値志向性とモデルフリー/モデルベース学習依存性との関係性に関する、非社会的な確率的状態遷移課題を用いた検討
Proselfs depends more on model-based than model-free learning in a non-social probabilistic state-transition task
*小口 峰樹(1)、李 楊(2,1)、松本 良恵(3,1)、清成 透子(4)、山本 和彦(5)、杉浦 繁貴(5)、坂上 雅道(1)
1. 玉川大学脳科学研究所、2. 名古屋大学大学院情報学研究科、3. 西南学院大学人間科学部、4. 青山学院大学社会情報学部、5. 株式会社コンポン研究所
*Mineki Oguchi(1), Li Yang(2,1), Yoshie Matsumoto(3,1), Toko Kiyonari(4), Kazuhiko Yamamoto(5), Shigeki Sugiura(5), Masamichi Sakagami(1)
1. Brain science institute, Tamagawa Univ, Tokyo, Japan, 2. Grad Sch of Informatics, Nagoya Univ, Nagoya, Japan, 3. Faculty of Human Sciences, Seinan Gakuin Univ, Fukuoka, Japan, 4. School of Social Informatics, Aoyama Gakuin Univ, Tokyo, Japan, 5. Genesis Research Institute, Aichi, Japan
Keyword: PROSOCIALITY, SOCIAL VALUE ORIENTATION, REINFORCEMENT LEARNING, MODEL-FREE/MODEL-BASED LEARNING
Humans form complex societies in which we routinely engage in social decision-making over the allocation of resources among ourselves and others. One dimension that characterizes social decision-making is whether to prioritize self-interest or respect for others (i.e., proself or prosocial). Researchers have defined these social preferences as social value orientation (SVO), which is a stable personality regarding how people evaluate self-prioritizing and other-respecting decisions in the allocation of resources in social settings. While some argue that such social decisions are made through specialized and modular mechanisms, others argue that they are made using domain-general learning mechanisms. There are at least two types of such domain-general decision-making systems; the “model-free” and “model-based” systems. The model-based system builds an internal model of the environment and selects actions that maximize rewards by learning state-action values while estimating state-transition probabilities. The model-free system reinforces and repeats the behavior that resulted in the reward, but does not learn the contingencies between states in the environment. If social decision-making relies on these complementary systems, then the inter-individual variability in prosociality should have some relationship to that in dependence on model-free/model-based systems. To investigate this hypothesis, we conducted an online experiment in which the participants were measured SVO and performed a sequential two-choice Markov decision task that allows us to assess the balance between model-free/model-based learning. In this task, the reward contingency is fixed for each state of the final choice, and that enable us to examine the change in the weight for model-based and model-free within an individual. The results showed that proselfs had larger mean reward gain in the early phase of the session than prosocials, and that the difference in reaction time due to learning different transition probabilities between states occurred earlier in proselfs than prosocials. Parameter estimation using reinforcement learning models showed that proselfs had a greater model-based dependence than prosocials in the early phase of the session. In the later phase of the session, the model-based dependence gradually decreased, and these differences between proselfs and prosocials became smaller. These analyses indicate that proselfs learned the task structure through model-based learning and thus arrived at the optimal options more quickly than prosocials, suggesting that there is a connection between inter-individual variability in SVO and that in model-based/model-free dependence. These results support the hypothesis that social decision-making uses domain-general learning mechanisms. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-111
社会的敗北の経験は腹側脚間核の縫線核投射細胞へのグルタミン酸作動性伝達の増強を引き起こす
The experience of social defeat induces the potentiation of glutamatergic transmission to raphe-projecting neurons in the interpeduncular nucleus.
*木下 雅恵(1)、岡本 仁(1)
1. 国立研究開発法人理化学研究所 脳神経科学研究センター 意思決定回路動態研究チーム
*Masae Kinoshita(1), Hitoshi Okamoto(1)
1. RIKEN CBS, Lab for Neural Circuit Dynamics of Decision Making
Keyword: social defeat, fighting behavior, interpeduncular nucleus, GluA1
Adult zebrafish establish dominant-subordinate relationship based on the result of fighting behavior. Our previous study showed the wining rate in fighting is regulated by habenula-interpeduncular nucleus (Hb-IPN) transmission. Here, we focused on the medial subnucleus of dorsal Hb (dHbM)-ventral IPN (vIPN)-median raphe (MR) pathway, which is activated in loser. Slice patch-clamp recordings from vIPN neurons revealed that only a part of neural population is highly responsive to glutamatergic inputs from the Hb. We investigated the axon morphology of recorded cells by biocytin loading with patch-clamp pipettes, and found that the majority of responsive population consists of efferent neurons relaying the dHbM input to the MR. We also recorded AMPAR-mediated miniature postsynaptic currents (AMPAR-mEPSCs) from MR-projecting vIPN neurons retrogradely labeled in acute slices, and compared properties of recorded currents between winner and loser. The frequency of AMPAR-mEPSCs was significantly higher in loser, but no difference was detected in the amplitude. On the other hand, the paired-pulse ratio of evoked EPSCs by electrical stimulation to the input fibers did not show the significant difference between winner and loser. These results suggest that the increase in the AMPAR-mEPSCs frequency in MR-projecting vIPN neurons reflects the increase in the number of active synapses on these neurons. Actually, Our previous data indicated activation of α7 nicotinic acetylcholine receptor by acetylcholine co-transmitted from the Hb promotes the recruitment of GluA1 subunit, which is thought to unsilence silent synapses, into postsynaptic membrane in vIPN neurons of loser. Taken together, it is suggested that the experience of defeat induces the potentiation of the dHbM-vIPN transmission by unsilencing of synapses on MR-projecting vIPN neurons. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-112
自閉スペクトラム症におけるZBTB16遺伝子変異の機能解析
Mutation of ZBTB16 in patients with autism spectrum disorder
*土井 美幸(1)、仲間 菜々子(1)、天野 元揮(2)、吉村 武(2)、片山 泰一(2)、臼井 紀好(1,2,3,4)、島田 昌一(1,2,3,4)
1. 大阪大学大学院医学系研究科、2. 大阪大学大学院連合小児発達学研究科 、3. 大阪大学国際医工情報センター 、4. 大阪精神医療センターこころの科学リサーチセンター
*Miyuki Doi(1), Nanako Nakama(1), Genki Amano(2), Takeshi Yoshimura(2), Taiichi Katayama(2), Noriyoshi Usui(1,2,3,4), Shoichi Shimada(1,2,3,4)
1. Grad Sch Med, Osaka Univ, Osaka, Japan, 2. United Grad Sch Child Dev, Osaka Univ, Osaka, Japan, 3. Global Cent Med Eng Info, Osaka Univ, Osaka, Japan, 4. Osaka Psych Res Center, Osaka Psych Med Cent, Osaka, Japan
Keyword: autism spectrum disorder
There is still no fundamental medication for autism spectrum disorder (ASD), thus it has expected that the elucidation of molecular mechanisms of ASD onset and pathology. In recent, the mutation (c.1319G>A;p.Arg440Gln) of Zinc finger and BTB domain containing 16 (ZBTB16) was identified found in ASD patients. ZBTB16 plays a role in neuronal proliferation and differentiation in early developmental stage. However, it is still unclear how ZBTB16 function is involved in ASD-related behaviors. Here, we demonstrated that an introduction of the mutation identified in ASD patients induced the reduction of expression level of ZBTB16. Thus, we analyzed the mouse behaviors using heterozygous Zbtb16 mutant mice that the expression level of ZBTB16 seems to be similar to ASD patients. As a result, in heterozygous Zbtb16 mutant mice, we observed impairment of social behaviors and increased repetitive behaviors compared with wild type (WT) mice, but no difference in anxiety-like behaviors. Our previous study shows that the body weight average of Zbtb16 KO mice was significantly decreased compared with WT mice due to skeletal defects, but that of heterozygous Zbtb16 mutant mice was no difference. According to our findings, heterozygous Zbtb16 mutant mice likely to be better suited for ASD model mouse than Zbtb16 KO mice. Our study is meaningful in terms of being able to simulate ASD-like behavioral characteristics using mouse model that mimic ASD patient, providing novel insights into ASD onset and/or pathology. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-113
自閉スペクトラム関連shank3ノックアウトマウスにおける社会性記憶障害と観察恐怖増加の神経メカニズムの解明
Neural mechanisms underlying social memory impairment and enhanced vicarious fear in autism-associated shank3 mutant mice
*ジョン ミョン(1,2)、今中 克俊(1,2)、黄 子彦(1,2)、度会 晃行(1)、王 牧芸(1)、田尾 賢太郎(1)、奥山 輝大(1)
1. 東京大学定量生命科学研究所、2. 東京大学大学院医学系研究科
*Myung Chung(1,2), Imanaka Katsutoshi(1,2), Ziyan Huang(1,2), Akiyuki Watarai(1), Mu-yun Wang(1), Kentaro Tao(1), Teruhiro Okuyama(1)
1. IQB, Univ of Tokyo, Tokyo, Japan, 2. Grad Sch Med, Univ of Tokyo, Tokyo, Japan
Keyword: Social behavior, Autism spectrum disorder, Social memory, Observational fear
Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental condition diagnosed by persistent deficits in social communication along with highly restricted, repetitive behaviors. Individuals with ASD have a higher prevalence of having comorbid neuropsychiatric conditions, such as social memory impairment and increased anxiety in various social situations. Recent studies revealed strong evidence of genetic contribution to ASD, particularly the genes that are essential for synapse formation and synaptic function. However, the common neural mechanisms which are responsible for the etiologies of both core and comorbid behavioral characteristics of ASD patients remain elusive. In this study, we found the shank3 knockout (Shank3-KO) mice, one of the most promising genetic ASD models, demonstrated social memory impairment and enhanced vicarious fear response in the observational fear task. Using the AAV-medicated CRISPR-Cas9 gene-editing technique, conditional knockout of shank3 in the hippocampal ventral CA1 subregion (vCA1), the social memory hub, successfully recapitulated the social memory impairment phenotype observed in the Shank3-KO mice. Together with the c-Fos expression screening experiment after the observational fear task and retrograde tracing experiment, a subgroup of bifurcating vCA1 neurons is suggested to have a possible involvement in the behavioral impairments of Shank3-KO mice. Further study will be focused on the functional contribution of multifurcate vCA1 neurons to the behavioral features of ASD, and to identify the physiological properties of these neurons during the observational fear task and the social memory task. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-114
腹内側前頭皮質への低頻度反復経頭蓋磁気刺激がサルの社交性に与える影響
Impact of low-frequency repetitive transcranial magnetic stimulation targeting the ventral medial frontal cortex on sociability in monkeys
*中村 晋也(1)、中村 元昭(2)、筒井 健一郎(1)
1. 東北大学 大学院生命科学研究科 脳神経システム分野、2. 昭和大学 発達障害医療研究所
*Shinya Nakamura(1), Motoaki Nakamura(2), Ken-Ichiro Tsutsui(1)
1. Laboratory of Systems Neuroscience, Graduate School of Life Sciences, Tohoku University, 2. Medical Institute of Developmental Disabilities Research, Showa University
Keyword: MONKEY, TRANSCRANIAL MAGNETIC STIMULATION, SOCIABILITY, DEPRESSION
The medial frontal cortex (MFC) has been consistently implicated in regulating emotion and sociability. Emerging evidence from human neuroimaging studies have demonstrated a unique functioning of the MFC subregions in regulation of sociability, yet the causal involvement remains to be fully elucidated. In this study, we aimed to causally examine how subregions of the MFC contribute to sociability by using inhibitory low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) in monkeys. Two Japanese monkeys (monkey A, female; monkey M, male) served in this study. We delivered LF-rTMS (1 Hz, 1200 pulses) targeting the ventral, dorsal or posterior part of the MFC. As a sham stimulation, we conducted the electrical stimulation of the scalp. To quantitatively evaluate changes in the sociability of the monkeys, we performed a sociability test, which quantified the monkeys’ behavior when the experimenter approached and stood in front of their home cages. As a result, we found a drastic change in their social attitude to the experimenter after LF-rTMS targeting the ventral MFC. We found a significant increase in the latency to approach the front side of the cage when the experimenter emerged in monkey M, but not in monkey A. The percent time spent near the experimenter significantly decreased in both monkeys. The percent time the monkeys oriented their faces toward the experimenter significantly decreased in monkey A, but not in monkey M. The percent time the monkeys oriented their bodies toward the experimenter significantly decreased in monkey A and marginally decreased in monkey M. The percent time the monkeys showed a straightly looking-down posture significantly increased in both monkeys. Although observed behavioral changes were slightly different between the two monkeys, it is conceivable that the level of sociability significantly decreased by LF-rTMS targeting the ventral MFC in both monkeys. On the other hand, we found no such significant changes in their behavior under the other stimulation condition. These results suggest the importance of the ventral MFC in regulation of sociability in monkeys. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-115
ゼブラフィッシュの社会性行動における小脳神経回路の機能
Function of the cerebellar neural circuitry in zebrafish social behavior
*保坂 栞(1)、日比 正彦(1)、清水 貴史(1)
1. 名古屋大学大学院理学研究科生命理学
*Shiori Hosaka(1), Masahiko Hibi(1), Takashi Shimizu(1)
1. Division of Biological Science, Graduate School of Science, Nagoya University
Keyword: Social behavior, Cerebellum, Zebrafish, Autism spectrum disorders
Social behavior is the interaction with other individuals, impaired in neurodevelopmental disorders such as autism spectrum disorders (ASDs). Since abnormalities in cerebellar morphology and function are observed in ASD patients, it has been considered the cerebellar neural circuitry is important for social behavior. However, it remains unknown how the cerebellum is involved in social behavior.
Zebrafish show social behavior called orienting behavior. It is a swimming behavior between two individuals: when they are spatially separated and can see each other, they approach and behave synchronously. In this study, we performed a social behavioral experiment to clarify the role of cerebellar neural circuits in the sociality. We used adult wild-type zebrafish, transgenic (Tg) zebrafish that express botulinum toxin (BoTx), which inhibits release of neurotransmitters, in either granule cells (GCs) or Purkinje cells (PCs), and reelin mutant zebrafish that show abnormal positioning of PCs. In spatially separated and visually recognizable condition, pairs of wild-type fish were in close proximity to the partition separating the two fish and exhibited a specific range of body angles (orienting angles) compared to the condition without visual stimuli. The Tg fish expressing BoTx in GCs or PCs, and the reelin mutant fish showed significantly reduced percentages of positioning near the partition and indicating the orienting angles in the presence of visual stimuli, compared to their siblings as controls. The data suggest that the zebrafish cerebellum plays important role in the social behavior.
In this study, the Tg fish expressing BoTx in GCs showed normal swimming behavior. However, average speed of free swimming was reduced in the Tg fish expressing BoTx in PCs and the reelin mutant fish, compared to controls. There is a possibility that they have abnormal motor ability and we cannot compare only social behavior with control. Therefore, we established new mutant zebrafish of genes specifically expressed in PCs. These include the glutamate receptor gene grid2, carbonic anhydrase 8 (ca8), which are related to human diseases, and we are conducting further social behavioral experiments with the mutants. Furthermore, we found the expression of immediate-early genes such as c-fos, which is an indicator of neuronal activity, was increased in the cerebellum during the social behavior. Further analysis will reveal how the zebrafish cerebellum controls sociality. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-116
群飼ケージ内で自由行動する複数サル個体の3Dマーカーレスモーションキャプチャー
3D markerless motion capture of multiple freely behaving monkeys in a group cage.
*松本 惇平(1,2)、兼子 峰明(3)、木村 慧(3)、Negrete Salvador (4)、橋本-須田 直子(5)、兼子 明久(5)、森本 真弓(5)、角谷 絵里(3)、西丸 広史(1,2)、瀬戸川 剛(1,2)、郷 康広(6,7)、柴田 智広(4)、西条 寿夫(1,2)、高田 昌彦(3)、井上 謙一(3)
1. 富山大学学術研究部医学系システム情動科学講座、2. 富山大学アイドリング脳科学研究センター、3. 京都大学霊長類研究所神経科学研究部門統合脳システム分野、4. 九州工業大学生命体工学研究科人間知能システム工学専攻、5. 京都大学霊長類研究所、6. 自然科学研究機構生命創成探究センター認知ゲノム研究グループ、7. 生理学研究所システム脳科学研究領域
*Jumpei Matsumoto(1,2), Takaaki Kaneko(3), Kei Kimura(3), Salvador Blanco Negrete(4), Naoko Suda-Hashimoto(5), Akihisa Kaneko(5), Mayumi Morimoto(5), Eri Sumiya(3), Hiroshi Nishimaru(1,2), Tsuyoshi Setogawa(1,2), Yasuhiro Go(6,7), Tomohiro Shibata(4), Hisao Nishijo(1,2), Masahiko Takada(3), Ken-ichi Inoue(3)
1. Dept System Emotional Sci, Faculty of Med, Univ of Toyama, Toyama, Japan, 2. Research Center for Idling Brain Sci, Univ of Toyama, Toyama, Japan, 3. Systems Neurosci Section, Dept Neurosci, Primate Research Inst, Kyoto Univ, Inuyama, Japan, 4. Dept of Human Intelligence Systems, Grad Sch Life Sci and Systems Engineering, Kyushu Inst of Tech, Kitakyushu, Japan, 5. Primate Research Inst, Kyoto Univ, Inuyama, Japan, 6. Cognitive Genomics Research Group, Exploratory Research Center on Life and Living Systems (ExCELLS), National Inst of Natural Sci, Okazaki, Japan, 7. Dept of System Neurosci, National Institute for Physiological Sci, Okazaki, Japan
Keyword: markerless motion capture, non-human primate, social behavior, deep learning
Monkeys form well-organized groups and make complex social decisions based on relationships between individuals and social contexts. Because of this sociality and the commonality of their brains with humans, the analysis of their behavior will be very useful for studying the neural mechanisms of human social behavior and its impairment in neuropsychiatric disorders. However, behavioral analysis of naturally behaving monkeys in a group usually requires manual counting of various behaviors, which has been a bottleneck in research due to problems in throughput and objectivity. We are developing a 3D markerless motion capture system for multiple monkeys for high-throughput, objective, and comprehensive analysis of social behavior through automation. The present system captured images synchronously from eight cameras installed in a group cage (4 x 4 meters) with four macaques. Artificial neural networks were trained and used to detect individual monkeys and estimate each individual's 2D pose and collar color (if visible) in 2D images from each camera. Then, matching of individuals between different cameras was performed based on the similarity of the 2D poses. The 3D poses were calculated with triangulation using matched 2D poses from multiple cameras. The association of individuals between frames was based on the 3D pose similarity. Finally, the motion of each individual was smoothed. The motion capture results were in agreement with visual observations, and 3D pose estimates with individual labels (the collar color) could be obtained for most of the time in a recording (82.6 % of time in a 30-min test video, average of N=4 monkeys). For the rest of the time, either a monkey was not detected (often because of severe occlusion), or the individual labels was not assigned to the track of a monkey (often because the collar was invisible for a relatively long period). We are currently evaluating the system's performance in more detail and analyzing the long-term data to quantify the relationships among individuals in a group and the individuality of social behavior. The present motion capture system will contribute to an automatic and objective analysis of various social behaviors in macaques and will be applicable to other primate species. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-117
自閉症モデルShank3変異マウスの腹側海馬における異常な社会性記憶表象と社会性記憶障害
Disrupted social memory ensembles in the ventral hippocampus underlie social amnesia in autism-associated Shank3 mutant mice
*田尾 賢太郎(1)、ジョン ミョン(1)、度会 晃行(1)、黄 子彦(1)、王 牧芸(1)、奥山 輝大(1)
1. 東京大学定量生命科学研究所
*Kentaro Tao(1), Myung Chung(1), Akiyuki Watarai(1), Ziyan Huang(1), Mu-Yun Wang(1), Teruhiro Okuyama(1)
1. IQB, Univ of Tokyo, Tokyo, Japan
Keyword: SOCIAL MEMORY, VENTRAL HIPPOCAMPUS, SHARP-WAVE RIPPLE
The ability to remember conspecifics is critical for adaptive cognitive functioning and social communication, and impairments of this ability are hallmarks of autism spectrum disorders (ASDs). Although hippocampal ventral CA1 (vCA1) neurons are known to store social memories, how their activities are coordinated remains unclear. Here we show that vCA1 social memory neurons, characterized by enhanced activity in response to memorized individuals, were preferentially reactivated during sharp-wave ripples (SPW-Rs). Spike sequences of these social replays reflected the temporal orders of neuronal activities within theta cycles during social experiences. In ASD model Shank3 knockout mice, the proportion of social memory neurons was reduced, and neuronal ensemble spike sequences during SPW-Rs were disrupted, which correlated with impaired discriminatory social behavior. The disruption of spike sequence consistency was not observed in the dorsal CA1 of Shank3-KO mice, indicating that the disruption is not a general phenomenon across the dorsoventral axis of the hippocampus, but it is specific to its ventral part. These results suggest that SPW-R-mediated sequential reactivation of neuronal ensembles is a canonical mechanism for coordinating hippocampus-dependent social memories and its disruption underlie the pathophysiology of social memory defects associated with ASD. Future work will need to determine how these social neuronal ensembles are coordinated in terms of identities of other individuals or sensory modalities of social perception. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-118
バソプレシン1b受容体およびオキシトシン受容体による雌マウス性行動の調節～性的受容性の二つの側面～
Regulation of female mouse sexual behavior by vasopressin 1b receptor and oxytocin receptor-two aspects of sexual receptivity-
*林 姫花(1)、清水 稀惠(2,3)、中村 和昭(2,3)、近藤 保彦(1)
1. 帝京科学大学大学院 理工学研究科、2. 国立成育医療研究センター薬剤治療研究部、3. 埼玉大学大学院理工学研究科
*Himeka Hayashi(1), Kie Shimizu(2,3), Kazuaki Nakamura(2,3), Yasuhiko Kondo(1)
1. Grad Sch Sci, Teikyo Univ of Sci, Yamanashi, Japan, 2. NCCHD, 3. Grad Sch Sci, Univ of Saitama, Saitama, Japan
Keyword: Vasopressin 1b receptor, female sexual behavior, sexual receptivity and proceptivity
Vasopressin and oxytocin as neuropeptide bind own receptors and regulate some social behaviors in rodents. In male mice, it has reported vasopressin receptor deficit facilitate male typical sexual behavior. Although female mice are enhanced lordosis by oxytocin administration, role of vasopressin and their receptors on female sexual behavior are still unclear. In this study, using vasopressin 1a, 1b receptor knockout respectively (aKO, bKO each), both 1a and 1b double knockout (dKO) and oxytocin receptor knockout (OTRKO) female mice, we compared to wild-type toward each genotype and investigated the relation between action of these neuropeptide receptors and female sexual behavior. In previous study, almost researcher could not judge whether female had showed lordosis or not because observation of sexual behavior using male home cage that move freely and their position aren’t fixed made it difficult. Now, we prepared two-storied cage which has narrow floor to observe from the side of moving mice. That enabled for us to measure lordosis correctly and we examined effect deficit of peptide hormone receptor affect on lordosis. Subject female were ovariectomized under isoflurane anesthesia and were used with injection hormones to be artificially estrous. Sexual behavior tests were carry out 3 times totally measuring number of lordosis female had showed when mounted by males and calculated lordosis quotient (LQ). In addition to LQ, an index of typical sexual receptivity of female, we also measured reject-like behavior pressing down male face and/or body to prevent male from approaching to evaluate other character of female sexual receptivity which is not just lordosis. As a results, while aKO express LQ as high as WT, bKO almost didn’t show lordosis and their LQ were significantly lower than WT. However, dKO who are lack of vasopressin 1b receptor showed lordosis are much as WT and significantly higher than bKO in spite of having no vasopressin 1b receptor likewise bKO. In contrast, it was no difference in LQ between OTRKO and WT; in other words OTRKO presented LQ as high as WT, but reject-like behavior toward approach from male significantly increased in OTRKO female. These results suggested that oxytocin receptor regulates reject-like behavior toward male mount, vasopressin 1a, 1b receptor are interacted with inactivation and activation of lordosis respectively. Consequently, female sexual receptivity is not as simple as if female show lordosis or not, it indicated that female sexual receptivity is consisted of two receptive aspects: to accept approach to lead to mount and to receive intromission involve penile insert led directly to fertilization and pregnancy. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-119
社会性記憶と情動情報を統合する神経メカニズムの解析
Neural mechanisms underlying the association of social memory with negative emotional valence
*須藤 成俊(1)、Mu-Yun Wang(1)、Myung Chung(1)、黄 子彦(1)、度会 晃行(1)、田尾 賢太郎(1)、奥山 輝大(1)
1. 東京大学定量生命科学研究所
*Narutoshi Suto(1), Mu-Yun Wang(1), Myung Chung(1), Ziyan Huang(1), Akiyuki Watarai(1), Kentaro Tao(1), Teruhiro Okuyama(1)
1. Institute for Quantitative Biosciences, Univ of Tokyo, Tokyo, Japan
Keyword: Social memory, emotional valence
The ability to recognize and respond appropriately to harmful and affiliative conspecifics is critical for the survival of social animals in their group. Animals avoid aggressor conspecifics and take affiliative behavior to non-aggressive ones. Commonly using the chronic social defeat-induced social avoidance behavioral paradigm, existing studies have uncovered the neural circuits for avoiding aggressor conspecifics. In the paradigm, the male C57BL/6J mice subjected to chronic subordination by a CD-1 male mouse (i.e., aggressor) avoid other conspecifics even including a non-aggressor mouse, which we termed “general social avoidance”. This behavioral phenotype is thought to be due to depression, and supporting this hypothesis, the defeated mice show another depression-like behavior marked by anhedonia and anxiety. Recent evidence shows that the expression of the general social avoidance by chronic social defeat is closely linked to stress-induced synaptic plasticity within a number of different brain regions, including Nucleus accumbens (NAc), Prefrontal cortex (PFC), and thalamus. Specifically, the defeated mice exhibit increased synaptic strength at intralaminar thalamus inputs to NAc medium spiny neurons. Also, higher PFC reactivity is observed in defeated mice. These results give insights into depression-based general social avoidance. However, little is known about how defeated animals avoid the specific individual that defeated them instead of all individuals, which we termed “specific social avoidance”. Here, we established a novel social defeat paradigm modified from the classical one, which enabled us to quantify the degree of the specific social avoidance. In this study, to uncover the neural circuit mechanisms underlying the specific social avoidance, we focused on the role of hippocampal ventral CA1 (vCA1) neurons essential for social memory. Using our novel behavioral paradigm combined with optogenetics and neurophysiological analysis, we found that vCA1 and its projection target had critical roles for animals in recognizing and avoiding a specific individual which is harmful to them. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-120
自身が有利な不平等への回避傾向とアルギニンバソプレシン受容体1a遺伝子(AVPR1A)との関連
Association of polymorphism in arginine-vasopressin receptor gene (AVPR1A) with advantageous inequity aversion
*田中 大貴(1)、仁科 国之(2)、寿 秋露(3)、高橋 英彦(4)、坂上 雅道(1)、松田 哲也(1)、井上-村山 美穂(5)、高岸 治人(1)
1. 玉川大学脳科学研究所、2. 大阪大学大学院人間科学研究科、3. 玉川大学脳科学研究科、4. 東京医科歯科大学大学院医歯学総合研究科、5. 京都大学野生動物研究センター
*Hiroki Tanaka(1), Kuniyuki Nishina(2), Qiulu Shou(3), Hidehiko Takahashi(4), Masamichi Sakagami(1), Tetsuya Matsuda(1), Miho Inoue-Murayama(5), Haruto Takagishi(1)
1. Brain Science Institute, Tamagawa University, Machida, Japan, 2. Graduate School of Human Sciences, Osaka University, Suita, Japan, 3. Graduate School of Brain Sciences, Tamagawa University, Machida, Japan, 4. Graduate School of Medical and Dental Sciences, Medical and Dental University, Tokyo, Japan, 5. Wildlife Research Center, Kyoto University, Kyoto, Japan
Keyword: prosocial behavior, inequity aversion, arginine-vasopressin receptor gene, economic game
Inequity aversion is a social preference for the distribution of rewards between self and others and it is important in the formation of cooperative societies. Inequity aversion comprises two types: aversion felt when one's gain is less than that of others, called disadvantageous inequity aversion (DIA), and when one's gain is more than that of others, called advantageous inequity aversion (AIA). Although many studies have focused on brain functions related to inequity aversion, few have examined the molecular mechanisms of inequity aversion. This study examined the association between the degree of inequity aversion estimated from behavior in five economic games and polymorphisms in three genes that are associated with human sociality. Adult participants (n = 420) in their 20s to 50s took part in multiple experiments. They engaged in prisoner's dilemma game, dictator game, public goods game, trust game, and ultimatum game in an anonymous situation, each on a different day. The DIA and AIA were calculated using Bayesian estimation from the behavior in five economic games. Polymorphisms in the oxytocin receptor gene (OXTR, rs53576), arginine-vasopressin receptor gene (AVPR1A, RS3), and μ-opioid receptor gene (OPRM1, A118G) were examined for their association with DIA and AIA. The results showed that for AVPR1A RS3, those with the SS genotype had a higher AIA than those with the SL or LL genotypes, but no association was found for DIA. Moreover, there was also no association with DIA and AIA for OXTR rs53576 and OPRM1A A118G. Their results indicate that the AVPR1A is important for human prosociality. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-121
胎生期におけるGABAA受容体アンタゴニストのピクロトキシン暴露による仔の自閉症様行動と異常な遺伝子発現
Exposure to GABAA receptor antagonist picrotoxin in pregnant mice causes autism-like behaviors and aberrant gene expression in offspring
*古田島 浩子(1,2)、萩原 英雄(3)、佐藤 敦志(1,4)、萩野 洋子(1)、田中 美歩(5)、加藤 喜久(1,6)、西藤 泰昌(1,7)、高松 幸雄(1,7)、内野 茂夫(2)、宮川 剛(3)、池田 和隆(1)
1. 東京都医学総合研究所依存性物質プロジェクト、2. 帝京大学理工学部バイオサイエンス学科、3. 藤田医科大学総合医学研究所システム医科学研究部門、4. 東京大学医学部付属病院小児科、5. 東京大学医学部付属病院精神神経科、6. 東京大学大学院医学系研究科、7. 東京都医学総合研究所基盤技術支援センター
*Hiroko Kotajima(1,2), Hideo Hagihara(3), Atsushi Sato(1,4), Yoko Hagino(1), Miho Tanaka(5), Yoshihisa Katoh(1,6), Yasumasa Nishito(1,7), Yukio Takamatsu(1,7), Shigeo Uchino(2), Tsuyoshi Miyakawa(3), Kazutaka Ikeda(1)
1. Addictive Substance Project, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan, 2. Department of Biosciences, School of Science and Engineering, Teikyo University, Tochigi, Japan, 3. Division of Systems Medical Science, Institute for Comprehensive Medical Science,Fujita Health University, Aichi, Japan, 4. Department of Pediatrics, The University of Tokyo Hospital, Tokyo, Japan, 5. Department of Neuropsychiatry, The University of Tokyo Hospital, Tokyo, Japan, 6. DeparGraduate School of Medicine, The University of Tokyo, Tokyo, Japan, 7. Center for Basic Technology Research, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan
Keyword: autism spectrum disorder, picrotoxin, GABAA receptor, social interaction
Autism spectrum disorder (ASD) is a neurodevelopmental disorder that is characterized by deficits in social interaction and restricted/repetitive behaviors. Symptoms of ASD are diagnosed during early childhood and remain during an individual’s life. The influence of γ-aminobutyric acid (GABA) during prenatal development is excitatory, and GABA/GABAA receptor signaling is important in cellular processes during development. However, whether and how disturbances of GABA signaling in embryos that are caused by GABAA receptor inhibitors cause ASD-like pathophysiology are poorly investigated. This study examined whether exposure to the GABAA receptor antagonist picrotoxin causes ASD-like pathophysiology in offspring by conducting behavioral tests from the postnatal 7 to 10-11 weeks of age and performing gene expression analyses in mature mouse brains. Here, we found that picrotoxin-exposed male mice exhibited a reduction of active interaction time in the social interaction test in both adolescence and adulthood. No significant difference was found between control and picrotoxin-exposed female mice in the social interaction test. The gene expression analyses showed that picrotoxin-exposed male mice exhibited a significant increase in the gene expression of odorant receptors. Weighted gene co-expression network analysis showed a strong correlation between social interaction and enrichment of the “odorant binding” pathway gene module. Our results suggest that exposure to a GABAA receptor inhibitor during the embryonic period induces ASD-like behavior, and impairments in odorant function may contribute to social deficits in offspring. We provide a better understanding of the pathophysiology of ASD and the prenatal inhibition of GABAA signaling may a mechanism that contributes to ASD. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-122
対人間の身体的距離が脳活動に与える影響：fNIRS研究
The effect of interpersonal physical distance on brain activity: An fNIRS study
*栗原 勇人(1)、大隈 玲志(1)、髙橋 徹(1)、三浦 哲都(1)、大須 理英子(1)
1. 早稲田大学
*Yuto Kurihara(1), Reiji Ohkuma(1), Toru Takahashi(1), Akito Miura(1), RIeko Osu(1)
1. Waseda University
Keyword: Interpersonal Physical Distance, fNIRS, Hyperscanning
Keeping proper physical distance between people is important during social interaction. When we are too close to each other physically, we often feel uncomfortable (i.e., invaded personal space). Further, in recent COVID-19 situation, wearing or not wearing a mask induce significant impact on physically close interaction. However, the effect of interpersonal physical distance and mask on brain activity is not fully unknown. In this study, we conducted functional near-infrared spectroscopy (fNIRS) scanning during face-to-face standing posture for eight participants (four pairs). We instructed participants to gaze your partner’s face during standing for 120 s. Each pair of participants stood either 20 cm (Near condition) or 70cm (Far condition) away from each other. They stood either with masks or without masks in the near and far distance conditions. After each trial, the participants were asked to answer the Visual Analog Scale (VAS) for discomfort. We measured cortical hemodynamics activity using fNIRS with a sampling frequency of 10.17 Hz. Each participant attached 8 sources and 8 detectors constructing 17 measurement channels (one of the detectors were assigned to short distance scalp signal detection). These fNIRS channels were placed over the prefrontal cortex (PFC) and right temporal-parietal junction (rTPJ). We measured changes in oxy-hemoglobin concentration and calculated intra-brain functional connectivity (FC) using Wavelet Coherence between rTPJ and left PFC, rTPJ and middle PFC, and rTPJ and right PFC, respectively. The two-way ANOVA of distance (near or far) × mask (no-mask or with-mask,) showed the significant interaction in FC between rTPJ and left PFC (F(1,7) = 15.0854, p = .006, ηp2=0.6830). The post-hoc analysis showed that, in the near distance condition, higher FC was significantly higher with mask than without mask; in no-mask condition, FC was significantly higher FC at near distance than far distance. There were no significant differences in FCs between rTPJ and middle PFC or right PFC. We also found a significantly negative correlation between rTPJ-left PFC FC and the degree of discomfort in pulled data (N = 8 participants × 2 mask conditions × 2 distance conditions = 32; r=-0.372, p=0.0362). These results may suggest that rTPJ-left PFC FC was related to interpersonal distancing. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-123
平常時と急性社会敗北ストレス下の睡眠・覚醒制御におけるマイクログリアの関与の可能性
Involvement of microglia in sleep/wake regulation in baseline conditions and under acute social defeat stress in mice
*宮西 和也(1,2)、船戸 弘正(2,3)、柳沢 正史(2,4,5)
1. 筑波大学グローバル教育院ヒューマニクス学位プログラム、2. 筑波大学国際統合睡眠医科学研究機構、3. 東邦大学医学部解剖学講座、4. テキサス大学サウスウウェスタンメディカルセンター分子遺伝学講座、5. 筑波大学生存ダイナミクス研究センター
*Kazuya Miyanishi(1,2), Hiromasa Funato(2,3), Masashi Yanagisawa(2,4,5)
1. Ph.D. Program in Humanics, School of Integrative and Global Majors, University of Tsukuba, 2. International Institute for Integrative Sleep Medicine, University of Tsukuba, Ibaraki, Japan, 3. Department of Anatomy, Faculty of Medicine, Toho University, Tokyo, Japan, 4. Department of Molecular Genetics, University of Texas Southwestern Medical Center, Texas, USA., 5. Life Science Center for Survival Dynamics, Tsukuba Advanced Research Alliance, University of Tsukuba, Ibaraki, Japan.
Keyword: MICROGLIA, SOCIAL DEFEAT STRESS, SLEEP, PLX
Microglia, the brain-resident macrophages, account for 10-15% of all cells in the adult brain. They produce inflammatory cytokines and remove dead cells and foreign materials against immune challenge. We previously found circadian changes in the morphology and function of microglia. In the prefrontal cortex, microglia displayed hyper-ramified morphology and increased phagocytosis of synapses during sleep. These results suggested that the circadian changes in microglial activity may contribute to sleep/wake behavior. However, whether and how microglia regulate sleep/wake behavior remains to be elucidated. Here, to examine the relationship between sleep/wake behavior and microglia, we employed the colony-stimulating factor-1 receptor antagonist PLX5622 (PLX), which depletes microglia. EEG/EMG recordings were performed after mice were fed with the PLX-formulated chow for 14 days. We found that PLX-treatment decreased wake amount and increased NREM sleep amount during dark phase in baseline conditions. To further investigate the role of microglia in sleep/wakefulness under acute social defeat stress (ASDS), which triggers a strong microglial activation as previously reported, we examined whether ASDS alters the effect of microglial elimination on sleep/wake behavior. Following the previous studies, C57BL/6N mice were briefly encountered with highly aggressive ICR mice 4 times during 1-hour ASDS session to minimize severe injury of defeated mice. We exposed mice with or without PLX-treatment to ASDS during ZT11-12 and then performed EEG/EMG recordings. We found that PLX-treatment further exacerbates ASDS-induced decrease in wake amount, suggesting that microglia may play a potentially protective role against ASDS. Taken together, our study indicated the possibility that microglia are involved not only in the regulation of sleep/wake behavior in baseline conditions, but also in sleep changes in response to mental stress. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-124
オスマウスのメス記憶に関与する側坐核の細胞集団
The nucleus accumbens for social memory of conspecific female
*度会 晃行(1)、石田 廉(1)、奥山 輝大(1)
1. 東京大学 定量生命科学研究所
*Akiyuki Watarai(1), Kiyoshi Ishida(1), Teruhiro Okuyama(1)
1. Institute for Quantitative Biosciences (IQB), The University of Tokyo
Keyword: Social memory, Ultrasonic vocalization, Sexual behavior, nucleus accumbens
哺乳類は種ごとに一夫一妻、一夫多妻、乱婚など異なる婚姻様式をとる一方で、多くのオスは交尾相手のメスを記憶・区別することにより、個々のメス個体に対して性行動の形式や量を適切に調節する。オスマウスは性行動の過程においてメスに対し超音波発声を示すが、新規なメスと既知のメスそれぞれに対する発声量を定量したところ、新規なメスに比べ既知のメスに対しての発声量がより少ないことが明らかになった。そのような社会性記憶に依存した超音波発声の減少は、数分で記憶したのちに短いインターバルを挟んでメスと再会する「短時間記憶課題」と、2時間で記憶したのちに長いインターバルを挟んで再会する「長時間記憶課題」の両者において観測された。そこで、側坐核(NAc)におけるCaMKII陽性細胞(NAc-CaMKII)、Drd1陽性細胞(NAc-Drd1)、およびDrd2陽性細胞(NAc-Drd2)の発声制御の機能を探索する目的で、メスを用いた短時間または長期時間記憶課題の最中に光遺伝学的手法により神経活動抑制を行なった。なお、光抑制はNAcに感染させたアデノ随伴ウイルス(AAV)により各細胞集団特異的に光感受性タンパクeArchTを発現させることで可能にした。NAc-CaMKIIの光抑制をした際には短時間および長時間記憶課題のいずれにおいても影響が見られなかったが、NAc-Drd1およびNAc-Drd2を光抑制した際には長時間記憶課題でのみ記憶に依存した超音波発声の減少が障害された。また、社会性記憶の保存領域である腹側海馬CA1領域(vCA1)の光抑制による超音波発声への影響は短時間記憶課題では見られず、長時間記憶課題においてのみ生じた。これらの結果に加え、先行研究によりvCA1からNAcへの投射回路は既知オス個体に対する接近の減弱に寄与することが示されていることから、長時間で形成された記憶による性行動の調節にはvCA1からの投射を受けるNAc-Drd1およびNAc-Drd2の活動が寄与していると考えられた。 | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-125
ラットにとって馴染みのない系統は全て同等ではない
Rats do not consider all unfamiliar strains equivalent
*清川 泰志(1)、向後 大樹(1)、黒田 菜穂子(1)、武内 ゆかり(1)
1. 東京大学獣医動物行動学研究室
*Yasushi Kiyokawa(1), Hiroki Kogo(1), Naoko Kuroda(1), Yukari Takeuchi(1)
1. Lab. Vet. Etho. UTokyo
Keyword: GROUP IDENTITY, SOCIAL SIMILARITY, GROUP PREFERENCE, EMOTIONAL DISCRIMINATION
Humans show distinct social behavior when we recognize social similarity in opponents that are members of the same social group. It has been demonstrated that humans show a preference and increase their empathic concerns about an unfamiliar individual if they recognize a certain level of social similarity with that individual. However, little attention has been paid to the role of social similarity in non-human animals. We previously found that the presence of an unfamiliar Wistar, Sprague-Dawley (SD), or Long-Evans (LE) rat, but not an unfamiliar Fischer 344 (F344) rat, mitigated stress responses in the Wistar subject rats. Examining the genealogy of these strains reveals that SD and LE rats are three quarters and half Wistar rats, respectively, whereas F344 rats were established independently of Wistar rats. It is therefore possible that the subject rats recognized social similarity to unfamiliar Wistar, SD, and LE rats. Here we assessed whether Wistar subject rats show distinct behavior toward these strains of rats. In Experiment 1, when the Wistar subjects were allowed to explore a pair of Wistar and F344 rats, a pair of SD and F344 rats, or a pair of LE and F344 rats, the subjects showed a preference for unfamiliar Wistar, SD, and LE rats over F344 rats. In contrast, the subjects did not show a preference when they explored a pair of Wistar and SD rats or a pair of Wistar and LE rats. These results suggest that the Wistar subjects recognized social similarity with unfamiliar Wistar, SD, and LE rats. In Experiment 2, the Wistar subjects were allowed to explore the same strain of two stimulus rats, one naïve to treatment and the other stressed via foot shocks immediately before the test. We found that the subjects were capable of discriminating unfamiliar Wistar and SD rats, but not unfamiliar F344 rats, based on their stress statuses. However, as opposed to the results in Experiment 1, the subjects could not discriminate between the naïve and stressed unfamiliar LE rats. We further confirmed that the LE subjects were capable of discriminating unfamiliar LE rats, but not unfamiliar Wistar rats, based on their stress statuses. Therefore, it is probable that the subjects required more similarity with other rats to discriminate based on stress status than to show a preference. Taken together, we concluded that rats do not consider all unfamiliar strains equivalent. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-126
ヘキサゴン型飼育ケージの開発：
個体間コミュニケーションの操作による社会適応メカニズムの解析
Hexagonal columnar animal cage:
Mechanism of social adaptation by controlling inter-individual communication in mice
*倉内 祐樹(1)、松田 慧悟(1)、太田 有起(1)、関 貴弘(1)、香月 博志(1)
1. 熊本大学 大学院生命科学研究部 薬物活性学
*Yuki Kurauchi(1), Keigo Matsuda(1), Yuki Ohta(1), Takahiro Seki(1), Hiroshi Katsuki(1)
1. Dept. Chemico-Pharmacol. Sci., Grad. Sch. Pharm. Sci., Kumamoto Univ., Kumamoto, Japan
Keyword: Social adaptation, Social communication, Animal cage
To be health, it is important to adapt to society in which everything communicates with each other. However, the mechanism of social adaptation is poorly understood due to the lack of established methodologies that control intra-individual communication. To solve this problem, we have developed the hexagonal columnar animal cage that can control communication within individual mice by using removal partitions. In the experiment, male ICR-, ddY- BALB/c-, and C57BL/6J-strains of mice were used to evaluate the relationship between contact conditions and depression in tail suspension test. In the group in which only three mice of the same strain were contacted (Group 1), the depression level of ICR mice was not different even when the contact conditions were changed. The depression levels of ddY mice were exacerbated when separated from each other by using partitions with or without punched holes. The depression levels of BALB/c mice were exacerbated only when isolated by using partitions without punched holes. On the other hand, the partition with punched holes reduced the depression levels in C57BL/6J mice. Next, to investigate the influence of intra-individual communication within diverse groups, same approach was conducted in a group of 3 mice consisting of ICR, ddY, and BALB/c strains (Group 2), and a group of 3 mice consisting of ICR, ddY, and C57BL/6J strains (Group 3). In Group 2, immobility time of ddY mice was reduced in contact condition using partition with punched holes, and the depression levels were also reduced compare to Group 1. In Group 3, contact conditions had no effect on the depression levels of each mice. However, compare to Group 1, the partition with punched holes reduced the depression levels of ddY mice. On the other hand, the depression levels of C57BL/6J mice were exacerbated when physically separated from each other by using partition with punched holes. These results indicate that restriction of physical communication exacerbates the depression levels of ddY mice; however, the non-contact stimuli from other strain mice reduced the depression levels. In addition, the non-contact stimuli from same strain mice reduced the depression levels of C57BL/6J mice. In conclusion, our hexagonal columnar animal cage revealed that there are various means of communication for adapting to society. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-127
マカクザルにおける社会的原因結果関係の学習途上での原因判断
Causal attribution to agents during learning of causal relations in social circumstances in macaques
*杉山 秀吾(1)、足立 雄哉(2)、藤巻 彰吾(1)、飯島 淳彦(2,3)、長谷川 功(2)
1. 新潟大学大学院 自然科学研究科 人間支援科学コース、2. 新潟大学大学院 医歯学総合研究科 神経生理学分野、3. 新潟大学 医学部 保健学科
*Shugo Sugiyama(1), Yusuke Adachi(2), Shogo Fujimaki(1), Atsuhiko Iijima(2,3), Isao Hasegawa(2)
1. Grad Sch Sci Tech, Niigata Univ, Niigata, Japan, 2. Dept Physiol, Grad Sch Med, Niigata Univ, Niigata, Japan, 3. Sch Health Sci, Niigata Univ, Niigata, Japan
Keyword: macaque monkey, social behavior, cognitive neuroscience
In social circumstances we distinguish effects of possible causal factors, including ourselves, other persons, and other entities, on the outcomes of events. Although there have been many reports about tendency of humans to attribute the cause of outcomes to agents (self, others, or virtual ones) or other entities, less is known in non-human primates. In this study, two macaque monkeys (Macaca fuscata) performed a behavioral task together in which they judged the relevance of agents (self, the other conspecific, and a virtual agent) or other objects to good or bad outcomes. In each event, an agent (one of the monkeys or a virtual agent on a computer monitor) touched an object on the monitor, and a good or bad outcome occurred (the feedback was given by juice reward and sounds). The probabilities of good or bad outcomes were set to be equal between agents and between objects. The property (good, bad, or irrelevant) of each agent or object to the outcome was fixed for several touch events and then randomly changed within a set of combinations of the properties that defined a task condition. After each touch event, one of the monkeys judged which of the agent or the object that were involved in the event was relevant to the outcome. The monkeys needed to adapt to the condition through a sequence of events and judgements because the task condition occasionally changed. Our preliminary results indicated that in the initial judgments just after the change of the task condition, where the condition was still unclear for the monkeys, both monkeys made more judgments in favor (judged an agent as relevant to a good outcome or as irrelevant to a bad outcome) of self or the other monkey than virtual agents, suggesting the tendency of monkeys when judging relevance of agents to outcomes in social circumstances. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-128
マウスの慰め様行動に関わる神経活動
Neural ensembles activities underlying consolation-like behavior in mice
*齋藤 遼(1)、Deependra Kumar(2)、船戸 弘正(2,3)、柳沢 正史(2)、饗場 篤(1)
1. 東京大学大学院医学系研究科、2. 筑波大学国際統合睡眠医科学研究機構、3. 東邦大学医学部
*Ryo Saito(1), Deependra Kumar(2), Hiromasa Funato(2,3), Masashi Yanagisawa(2), Atsu Aiba(1)
1. Graduate School of Medicine, University of Tokyo, Tokyo, Japan, 2. International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Ibaraki, Japan, 3. Department of Anatomy, Toho University
Keyword: CONSOLATION, NEURAL ACTIVITY
Consolation behavior in humans is affiliative physical contact, for example, embracing to reduce pain or stress experienced by another individual. Rodents display increased allogrooming, a consolation-like behavior toward distressing members of the same species (Burkett et al., Science. 2016; Wu et al., Nature. 2021). Recent studies suggest that neural activity in the anterior cingulate cortex (ACC) is associated with consolation behavior but mainly in monogamous rodents (Burkett et al., Science. 2016; Li et al., eLife. 2021).
In this study, we studied consolation-like behavior in non-monogamous inbred mice. Firstly, we observed increased allogrooming behavior in bystander mice toward a conspecific animal experiencing pain by injection of honeybee toxin into the hind paw. Next, to understand the neural mechanisms of consolation-like behavior, we analyzed ongoing neural activity (calcium imaging) in ACC during allogrooming toward non-monogamous mice in pain. Furthermore, we aim to inhibit ACC neurons optogenetically during allogrooming to find the necessity.
The basolateral amygdala (BLA) and the nucleus accumbens (NAc) are two crucial downstream brain regions involved in the processing of empathic behavior (Allsop et al., Cell. 2018; Smith et al., Science. 2021). The ACC to BLA projection is necessary for the contagion of fear, and the ACC to NAc projection is required for the social transfer of pain. In the future, we plan to verify whether consolation-like behavior in non-monogamous mice requires ACC projections to BLA or NAc using in vivo calcium imaging and optogenetic manipulation.
Recognizing and sharing the affective state of others plays a crucial role in social communications in daily life. Our study will shed light on the neural basis of consolation behavior in understanding the human mind and the neural mechanisms of pro-social behavior. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-129
① 雌への注意 --- 視床網様核が司る交尾行動成立への影響 ---
Attention to a female --- Involvement of the thalamic reticular nucleus in the establishment of mating behavior ---
*稲森 俊之介(1,2)、高田 則雄(2)、田中 謙二(2)
1. 慶應義塾大学大学院薬学研究科、2. 慶應義塾大学大学院医学研究科
*Syunnosuke Inamori(1,2), Norio Takata(2), Kenji F Tanaka(2)
1. Grad Sch Pharm Sci, Keio Univ, Tokyo, Japan, 2. Grad Sch Med, Keio Univ, Tokyo, japan
Keyword: Thalamic reticular nucleus, Mating behavior, Attention, Optogenetics
An adult male mouse starts mating behavior within a few tens of minutes when a female mouse in estrus is placed in the same cage. For the initiation of the mating behavior, the male mouse first needs to recognize and pay attention to the female mouse as the mating target. In addition to sensory information about the female mouse, there is a variety of other perceptual information in the cage, such as environmental sounds and tactile sensations on the floor. What kind of activity does the brain of a male mouse show when the male pays attention to the female mouse? It is believed that the thalamic reticular nucleus (TRN) inhibits other information input when paying attention to specific information. The TRN allows to focus on what is most important at a given time among a variety of sensory stimuli. We hypothesized that the TRN is involved in "attention to a female", which is a condition for mating behavior. Experiments were conducted in 3-12 month old male mice. Parvalbumin (PV)-positive neurons are predominantly expressed in TRN. To observe intracellular Ca2+ fluctuations in TRN PV-positive neurons, we crossbred PV-tTA mice (Sasaki et al. 2012 PNAS) with tetO-YCnano50 mice (Kanemaru et al. 2014 Cell Rep). We then obtained PV-tTA::tetO-YCnano50 mice using the tetO system. To capture PV neural activity during mating behavior, fiber photometry measurements were performed to analyze male mating behavioral characteristics in five stages (approach, active mounting, passive mounting, pelvic thrust, and ejaculation). Next, PV-tTA::tetO-ArchT-EGFP mice were obtained by crossbreeding PV-tTA mice with tetO-ArchT-EGFP mice for optogenetic suppression of TRN PV-positive neuronal activity (Abdelaal in press). We optogenetically suppressed TRN activity during mating behavior and investigated how the amount of time spent per hour on mating behavior changed. The TRN activity of males was significantly altered for each mating behavioral characteristics. Optogenetic suppression of TRN activity at the moment of approaching the female mouse interrupted the behavior. Correspondingly, the number of mountings per hour and intravaginal ejaculation latency time decreased significantly. Optogenetic suppression of the TRN during mounting and pelvic thrust didn’t interrupt mating behavior, and there was no significant difference in intravaginal ejaculation latency time. These results indicate that TRN activity influences the maintenance and establishment of mating behavior. In addition, optogenetic suppression during approach affected maintenance of it, suggesting that the TRN is involved in "attention to a female”, and it is necessary for the establishment of mating behavior. In the future, we aim to study (1) the effects of optogenetic stimulation using ChR2 on behavior and (2) activity measurement and optogenetic manipulation for each TRN subdomains. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-130
Lack of efficacy for bremelanotide (Vyleesi) or melanocortin 4 (MC4R) receptors in the nucleus accumbens to enhance sexual motivation in female Syrian hamsters
*Johnathan M Borland(1), Abigail Kohut-Jackson(1), Anna Peyla(1), Megan Hall(1), Robert L Meisel(1)
1. University of Minnesota, Department of Neuroscience, Minnespolis, MN USA
Keyword: Social reward, Nucleus accumbens, Female sex behavior, melanocortin
For men sexual dysfunction is typically represented by performance issues (e.g., erectile problems); whereas for women, low levels of sexual desire and interest are primarily reported. Characterized by diminished interest, disinclination to initiate, and a loss of pleasure during sex; disorders of sexual desire among women are not only poorly understood from a psychological perspective, but also in terms of their underlying neurobiology. This loss of sexual desire is a source of distress for many women resulting in issues of low self-esteem and relationship conflict. This led to approval of the drug bremelanotide, trade name Vyleesi, to treat hyposexual desire disorder in women. However, despite approval, there is disagreement regarding the clinical efficacy of bremelanotide and almost nothing is known about its potential mechanism of action. Bremelanotide is a mixed melanocrotin receptor agonist, acting in the brain via MC3 and/or MC4 receptors. Thus, we investigated the role of bremelanotide in a female Syrian hamster model of sexual reward. Further, we examined the possibility that MC4 receptors could be regulated by female sexual experience. Female hamsters were given five, two or zero 10-min weekly sexual interactions in the conditioned place preference arena. This treatment regimen is clinically relevant as women are instructed to self-inject bremelanotide prior to engaging in sex. Females that experienced two 10-min interactions were also subdivided into groups that received i.p. saline, 50 ug/kg or 200 ug/kg bremelanotide 30-min prior to sexual experiences. Two or five days of sexual experience resulted in an increase in conditioning to the chamber in which the females had sex (p = 0.017 and p < 0.001). However, neither a low (50ug) nor a high (200ug) systemic dose of bremelanotide enhanced sexual reward (p > 0.050). Bremelanotide also failed to enhance sexual behavior, as there were no changes in the display of the female’s sexual behavior posture (p > 0.050). Following assessment of sexual reward, brains were collected for assessment of MC4 receptor in the striatum. Dopamine 1, 2 and MC4 receptor mRNA expression were analyzed using Syrian hamster customized RNAscope probes. Collectively, these studies do not provide basic research support for the clinical effectiveness of bremelanotide to enhance sexual motivation in women, nor do they support a role for MC4R expression in the nucleus accumbens mediating sexual reward in females. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-131
マウス視索前野で巣作り行動特異的にc-Fosを発現した神経細胞の性質
Characterization of nest-building specific c-Fos expressing neurons in the mouse preoptic area
*田川 菜月(1)、恒岡 洋右(2)、森 啓太(3)、古戎 道典(4)、船戸 弘正(2)、飯野 雄一(3)
1. 東邦大学大学院医学研究科、2. 東邦大学医学部、3. 東京大学大学院理学系研究科、4. 東京大学大学院医学系研究科
*Natsuki Tagawa(1), Yousuke Tsuneoka(2), Keita Mori(3), Michinori Koebis(4), Hiromasa Funato(2), Yuichi Iino(3)
1. Grad Sch Med, Toho Univ, Tokyo, Japan, 2. Sch Med, Toho Univ, Tokyo, Japan, 3. Grad Sch Sci, Univ of Tokyo, Tokyo, Japan, 4. Grad Sch Med, Univ of Tokyo, Tokyo, Japan
Keyword: Nest building, preoptic area, hypothalamus
Nest building is an innate behavior widely observed throughout the animal kingdom. Nests are built for thermoregulation, self-defense and breeding and enable the animal to increase their survival rate and reproductive success. The nest-building behaviors in mice are also innately motivated by multiple conditions, such as pre-sleep, parenting, and thermoregulation. Most of the innately motivated behaviors in mice are shown as stereotyped patterns, while nest building requires a certain degree of flexibility in adapting to the various nest materials. Nest building should be unique among the innate behaviors in that it is driven by multiple motivation, and that it shows flexibility on the use of nest material, and the neural basis of the nest building behavior in mice is the attractive model to understand the mechanism of the innate behaviors.
In hypothalamus, some regions have been known as the essential brain area regulating parental behaviors, sleep-wakefulness and thermoregulation. These behaviors and physiologies can affect the motivation of the nest building, so we hypothesized that some hypothalamic areas have any roles on regulating nest-building behaviors as well as other innate behaviors. In this study, we histologically elucidated neural activation on the brain areas in the hypothalamus during nest building.
Before histological analysis, we had confirmed that removing the nest bedding and introducing hardened nest material to the home cage induced the nest-building behavior within an hour, without thermal change or parental stimulation. Two hours after this procedure, we sampled their brains. The brains were cryosectioned, and the sections were proceeded to the multiple staining of in situ hybridization (ISH) and c-Fos immunohistochemistry. For ISH, the expression of Vglut2 and Vgat mRNAs were detected to identify the excitatory and inhibitory neurons, respectively. As a result, c-Fos positive neurons were observed in some hypothalamic areas including preoptic area, which were also known as important area for parental behavior, thermoregulation and sleep-wakefulness. Detailed histological analysis would characterize the c-Fos expressing neurons and provide important insights to understand the mechanism of nest building behavior. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-132
背側縫線核-前帯状皮質セロトニン作動性ニューロンの光遺伝学的操作による動的相互作用とその神経基盤の解析
Analysis of dynamic interactions and their neural underpinnings by optogenetic manipulation of dorsal raphe nucleus-anterior cingulate cortex serotonergic neurons
*畦地 裕統(1,2)、高橋 晋(1)
1. 同志社大学脳科学研究科認知行動神経機構部門、2. 同志社大学研究開発推進機構
*Hirotsugu Azechi(1,2), Susumu Takahashi(1)
1. Laboratory of Cognitive and Behavioral Neuroscience, Graduate School of Brain Science, Doshisha University, Kyoto, Japan, 2. Organization for Research Initiatives and Development, Doshisha University, Kyoto, Japan
Keyword: Serotonin, Anterior Cingulate Cortex, Optogenetics, Dynamic Interaction
Serotonin regulates various brain functions such as mood, sleep, and cognition, and consequently, it also influences social behavior. Most serotonergic neurons originate in the raphe nucleus in the midbrain and brainstem and project to widely distributed brain regions, with serotonergic neurons projecting from the dorsal raphe nucleus (DRN) to the anterior cingulate cortex (ACC) are thought to contribute to the control of sociability. However, it is unclear what is neural underpinning the regulation of sociability and how serotonergic neurons are involved in this neural underpinning. In addition, most of the social behaviors conventionally evaluated are based on a method in which only one rodent to be evaluated can behave freely, such as a three-chamber test, and behaviors in dynamic interactions among multiple rodents in which they are allowed to move around freely have not been evaluated. This study optogenetically stimulated DRN-ACC serotonergic terminals and recorded electrophysiology during dynamic interactions. For that purpose, we first generated mice expressing serotonergic neuron-specific channelrhodopsin (ChR2) by double infection of DRN with two types of adeno-associated viruses: one expressing floxed-ChR2 and the other expressing Cre recombinase under the tryptophan hydroxylase 2 (TPH2) promoter. A microdrive with tetrodes and optical fibers was then implanted in the ACC to allow optical stimulation and electrophysiological recordings during behavior. We conducted an open-field test of multiple animals to investigate behavioral changes such as approach/avoidance, locomotor activity, and grooming during dynamic interactions. Animal behavior was tracked using the multi-animal project of DeepLabCut, a markerless animal posture estimation tool. In this presentation, we will report and discuss the currently being analyzed results. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-133
社会的フィードバックによる鳴禽の発声条件づけ
Social feedback can condition vocal behavior in songbird
*橘 亮輔(1)、池渕 万季(2)、岡ノ谷 一夫(1,2)、柳原 真(3)
1. 東京大学、2. 理化学研究所、3. 帝京大学
*Ryosuke O Tachibana(1), Maki Ikebuchi(2), Kazuo Okanoya(1,2), Shin Yanagihara(3)
1. University of Tokyo, 2. RIKEN, 3. Teikyo University
Keyword: VOCAL EXCHANGE, SOCIAL BEHAVIOR, OPERANT CONDITIONING
Does social interaction modulate vocal behavior? Vocal communication is essential for social associations. Learning when and how to vocalize should be adaptively shaped by social context to maintain relationships in the community. We addressed this issue by examining socially motivated vocal conditioning on a songbird species, zebra finches (Taeniopygia guttata). This bird vocalizes specific calls to evoke other conspecifics' social responses, e.g., gathering each other, suggesting that they can associate such social feedback with their own vocalization. The present study tested whether zebra finches learn to facilitate and/or suppress vocalization according to social feedback. We performed an operant conditioning of vocal behavior by rewarding birds with social contact, in which the bird can briefly see its cagemate when the bird vocalizes in response to a non-vocal sound stimulus. Additionally, an LED light with different colors was provided as a context cue just before presenting the sound stimulus. The LED color indicated vocal-reward associations; one color implied the presence of social reward for correct vocalization, while the other suggested the absence of reward. A few weeks of conditioning with several hundred trials resulted in birds' vocalizing in response to the sound cue. Some of them tended to vocalize more for rewarded LED conditions than unrewarded conditions. These results demonstrate that zebra finches can learn the association between vocalization and social feedback, suggesting that social interaction modulates vocal behavior. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-134
Tickling differentially modulates activity in rat anterior insula
*Sarah Dagher(1), Shimpei Ishiyama(1)
1. Institute of Pathophysiology, Universitaetsmedizin der Johannes Gutenberg Universitaet Mainz, Mainz, Germany
Keyword: Tickling, Insula, Ultrasonic vocalizations, Social play
Since Darwin described diverse biological aspects of emotions, understanding internal states has become one of the major challenges with lots of debate on emotions definition and their expression across species. Yet, brain mechanisms underlying internal states that drive evolutionary conserved behaviours remain elusive. Ticklishness is a peculiar sensation seen in social species from rodents to humans. When tickled, rats emit appetitive 50 kHz ultrasonic vocalizations, in addition to pronounced chasing behaviour, emphasizing the rewarding nature of tickling. Previous work showed the activation of the trunk somatosensory cortex (S1) in response to tickling. Microstimulation in S1 deep layers equally evokes vocalizations (Ishiyama & Brecht, 2016). It is, however, unknown how the tickle tactile sensation is coupled to a positive emotional state. In this study, we focus on the insula being a central hub for emotional processing and receiving many inputs from sensory areas. In vivo freely-moving extracellular recordings revealed activation of insular neurons during tickling, with a notable effect seen in layer 2/3 of the dysgranular insula. Moreover, insula’s subdivisions showed distinct responses to tickling different body parts. Population firing rate of insula neurons increased ~ 70 ms before vocalization onset. Insula activity further increased upon vocalization offset, with the most prominent effect seen in layers 4 and 6 of the granular insula but not in layer 5. Clustering of peri-stimulus time histogram revealed differential response patterns to vocal emission, with one cluster showing inhibition during vocalization. Our preliminary results suggest that the insula might be implicated in the processing of ticklishness and vocalizations. We will further continue investigating potential circuits involved in the modulation of ticklish emotional response. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-135
健常な日本人女性におけるRELN rs7341475遺伝型と脳構造の関連
RELN rs7341475 associates with brain structure in healthy Japanese females
*山口 涼(1)、松平 泉(2)、竹内 光(3)、今西 規(4)、木村 亮介(5)、富田 博秋(6)、川島 隆太(2,3,7)、瀧 靖之(1,2)
1. 東北大学加齢医学研究所臨床加齢医学研究分野、2. 東北大学スマート・エイジング学際重点研究センター、3. 東北大学加齢医学研究所認知機能発達寄附研究部門、4. 東海大学医学部情報生物医学研究室、5. 琉球大学大学院医学研究科人体解剖学講座、6. 東北大学病院精神科、7. 東北大学加齢医学研究所応用脳科学研究分野
*Ryo Yamaguchi(1), Izumi Matsudaira(2), Hikaru Takeuchi(3), Tadashi Imanishi(4), Ryosuke Kimura(5), Hiroaki Tomita(6), Ryuta Kawashima(2,3,7), Yasuyuki Taki(1,2)
1. Department of Aging Research and Geriatric Medicine, Institute of Development, Aging and Cancer, Tohoku University, Miyagi, 2. Smart-Aging Research Center, Tohoku University, Miyagi, 3. Division of Developmental Cognitive Neuroscience, Institute of Development, Aging and Cancer, Tohoku University, Miyagi, 4. Biomedical Informatics Laboratory, Department of Molecular Life Science, Tokai University School of Medicine, Kanagawa, 5. Department of Human Biology and Anatomy, Graduate School of Medicine, University of the Ryukyus, Okinawa, 6. Department of Psychiatry, Graduate School of Medicine, Tohoku University, Miyagi, 7. Department of Advanced Brain Science, Institute of Development, Aging and Cancer, Tohoku University, Miyagi
Keyword: temperament, reelin, gray matter, cortical morphology
【背景】
ヒトの思考や行動の多様性は、個人に特徴的な心理的特性である「パーソナリティ」として説明することができる（Larsen and Buss. 2010）。気質とは、ヒトのパーソナリティの生得的な側面と考えられているが、胚発生に関与するタンパク質との関連は不明である。RELN遺伝子にコードされるReelinは、神経細胞の移動やシナプスの形成を介して、脳の発達に重要な役割を果たすタンパク質である。本研究では、ヒトのパーソナリティの形成におけるReelinの役割を明らかにすることを目的として、統合失調症の女性特異的な危険因子として検出された一塩基多型であるRELN rs7341475（G/A)（Shifman et al. 2008）と、女性の脳構造、および気質の関連を調べた。
【方法】
健康な日本人女性680名を本研究の対象とした。RELN rs7341475の遺伝型を調べ、4つの気質（新奇性追求、損害回避、報酬依存、持続）を評価する尺度である日本語版Temperament and Character Inventory（Cloninger et al. 1993, 木島 他, 1996）への回答を求めた。磁気共鳴画像（Magnetic Resonance Imaging; MRI）によって撮像したT1強調画像を用いて、局所灰白質体積（regional gray matter volume; rGMV）および大脳皮質形態を定量した。全脳を解析対象とした共分散分析を行い、rGMVと大脳皮質形態におけるリスク遺伝型（G/Gホモ接合体）と非リスク遺伝型（A/Gヘテロ接合体およびA/Aホモ接合体）の違いを調べた。また、4つの気質に対する遺伝型間の群間差をマンホイットニーのU検定によって調べた。さらに、重回帰分析によって、4つの気質とrGMVの関連を調べた。
【結果】
リスク遺伝型群は、いくつかの脳領域、特に両側の帯状回および側頭回において、非リスク遺伝型群と比較して有意に大きなrGMVを示した。また、リスク遺伝型群は非リスク遺伝型群よりも、左の外側後頭皮質の表面構造が有意に複雑であることが確認された。さらに、新奇性追求が右の上側頭回のrGMVと有意な正の相関があり、rs7341475遺伝型間でrGMVの差異が検出された領域と部分的に重なることが明らかとなった。
【結論】
本研究は、日本人女性の脳構造の個体差にRELN rs7341475が寄与していることを示した初めての研究である。rs7341475は統合失調症の危険因子として検出された一塩基多型であるが、健常者においても脳構造にこの多型が関与することが明らかとなった。本結果は、RELN rs7341475がヒトのパーソナリティの多様性および健常者における統合失調症に対する脆弱性を反映している可能性が示唆された。 | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-136
老齢マウスの機能的結合とMRIによって計測される付加的要因
Functional connectivity and additional factors measured by MRI in aged mice
*釣木澤 朋和(1,2)、領家 梨恵(3)、川島 隆太(3)
1. 産業技術総合研究所、2. 筑波大学大学院システム情報系、3. 東北大学加齢医学研究所
*Tomokazu Tsurugizawa(1,2), Rie Ryoke(3), Ryuta Kawashima(3)
1. National Institute of Advanced Industrial Science and Technology (AIST), 2. Faculty of Engineering, Information and Systems, University of Tsukuba, 3. Institute of Development, Aging and Cancer, Tohoku University
Keyword: aging, MRI, diffusion MRI, T2 relaxation
Recent MRI studies investigated the effect of aging on functional connectivity in the brain. However, it has not been investigated that additional age-related factors (e.g. glymphatic system, cell density, and iron distribution) in combination with functional connectivity for comprehensive understanding of aging brain. We previously showed that diffusion MRI could detect altered water diffusion in the tissue by inhibition of aquaporin-4, which is a water channel and is related to the glymphatic system and astrocyte volume change. Additionally, T2 relaxation time is also sensitive to the tissue water, cell density, and iron distribution in the brain, which is potentially affected by aging. In the current study, we aimed to investigate the effect of aging on tissue water diffusion, T2 relaxation, and proton density in addition to resting state functional connectivity. MRI acquisition was conducted at 7 T MRI system with a volume coil. Mice were anesthetized with low dose of medetomidine and isoflurane. The respiration was monitored, and the temperature was maintained by circulating hot water throughout the experiment. Apparent diffusion coefficient (ADC), which indicates tissue water diffusion, was measured by diffusion-weighted MRI. T2 relaxation time and proton density was measured using multi-slice multi-echo sequence. The ADC and T2 relaxation in the cerebral cortex, the hippocampus, and the striatum was compared between young and aged mice. Aged group resulted in significant decrease of ADC in the striatum. Reduction of ADC in the cerebral cortex was not significant, but the average of ADC in aged group was smaller than that of young group. Aged group also resulted in significant decrease of T2 relaxation time in the cerebral cortex and in the striatum. We will show the relationship between functional connectivity and additional age-related factors. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-137
Mapping Brain-wide Excitatory/Inhibitory Input Patterns Throughout the Mouse Lifespan
*Jayoung Kim(1,2,4), Yoon Kyoung Choi(1,4), Hyungju Jeon(1), Jihyun Kim(1,3), Jinhyun Kim(1,2,3)
1. Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul, South Korea, 2. Division of Bio-medical Science and Technology, KIST School, Korea University of Science and Technology (UST), Seoul, South Korea, 3. Department of Integrated Biomedical and Life Sciences, Graduate School, Korea University, Seoul, South Korea, 4. These authors contributed equally to this work
Keyword: Excitatory-inhibitory balance, lifespan, brain-wide, presynaptic input
Excitatory-Inhibitory (E-I) balance indicates the homeostasis of E-I synaptic activity in the neural network. As this balanced state is critical to the operation of normal brain functions, its disruption has been reported as an indicating factor for neurodegenerative and neurodevelopmental disorders. For example, E-I imbalance in the striatum of Parkinson’s Disease models has been associated with impaired motor function, while Autism Spectrum Disorder has been linked with increased excitation in the prefrontal cortex. Despite an increasing body of studies,brain-wide information of E-I characters throughout the lifespan remains unknown.
The aim of this study is to provide meso-scale maps of synaptic E-I input patterns of the mouse brain across its lifespan. Brain wide serial immunohistochemical staining of representative key molecules, such as vGluT and vGAT, was selected as a means to map presynaptic inputs. Brains from 9 age points were serially sectioned, stained, and imaged using fluorescent microscopy. These images were processed for 2D alignment and 3D-volume reconstruction for segmentation. Input ratios were then analyzed by comparing signal intensities of the antigens.
Preliminary results identified each brain region’s balanced state, revealing anatomically segmented patterns. Interestingly, these segmentations highly correlated with widely accepted parcellations of Allen Brain Map, suggesting E-I input patterns as a novel yet complying parameter to investigate the brain. Age-dependent changes were also revealed, such as a decrease of inhibitory input to the basal ganglia, hinting at functional alterations. Further in depth analysis is planned to capture even minute changes in subregions. Our study is to provide a set of atlases offering a comprehensive brain-wide view on region, age, and disease-model dependent comparisons of E-I input patterns, and possibly facilitate insight on underlying neural mechanisms. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-138
養育態度の解剖 -養育の質の世代間伝達と子どもの脳発達の関連-
Intergenerational transmission of parental care associates with brain structure in Japanese young adults.
*松平 泉(1)、山口 涼(1)、竹内 光(1)、川島 隆太(1)、瀧 靖之(1)
1. 東北大学
*Izumi Matsudaira(1), Ryo Yamaguchi(1), Hikaru Takeuchi(1), Ryuta Kawashima(1), Yasuyuki Taki(1)
1. Tohoku University
Keyword: intergenerational transmission, parenting, gray matter volume, MRI
【背景】 親の養育態度は子どもの脳発達に影響することが明らかにされている[Matsudaira et al., 2016など]。養育態度は親自身が過去に受けた養育を反映しやすく、世代間伝達を呈すると言われている[Belsky et al., 2009]。虐待被害者が自身の子どもを虐待しやすいことが広く報告されているが、近年のメタ解析によって効果量の小ささが確認されている[Madigan et al., 2019]。したがって、養育態度には親自身の被養育経験が反映される場合と、他の要因によってその影響が薄れる場合があると考えられるが、その差異が子どもの脳発達へどのように関与するかは、未だ明らかにされていない。そこで本研究では、親のポジティブな養育態度（暖かさ、親密さなど）の世代間伝達の有無と子世代の脳構造の関連を検討した。 【方法】 18歳から27歳の日本人149名とその両親を本研究の対象とした。以下、子世代をGeneration3 (G3)、両親世代をGeneration 2 (G2)、両親の親世代(子世代にとっての祖父母)をGeneration 1 (G1)と表現する。Parental Bonding Instrument日本語版の養護性指標(Care factor; CA)を用いて、G3にはG2父母の、G2にはG1父母の暖かさや親密さを回顧的に評価させた。CAの得点の中央値を基準として、G1・G2ともCAが高い群（肯定的伝達群）、G1のCAは低いがG2のCAは高い群（否定的伝達回避群）、G1・G2ともCAが低い群（否定的伝達群）、G1のCAは高いがG2のCAは低い群（肯定的伝達断絶群）、の4群にG3を分類した。磁気共鳴画像装置を用いてG3の脳のT1強調画像を撮像し、局所灰白質体積(regional gray matter volume; rGMV)を算出した。上述の4群間でrGMVに有意な差が見られる領域を明らかにするために、G3の年齢・性別・全頭蓋内容量を補正した一元配置分散分析を行った。 【結果】 G1父(G3にとっての祖父)のCAが低くG2母のCAが高い群（G1父→G2母の否定的伝達回避群）は、G1父からG2母に高いCAが伝達されている群（G1父→G2母の肯定的伝達群）よりも、右中側頭回のrGMVが有意に小さいことが確認された（peak voxelの座標[x, y, z]=[57, -26, -14]; P = 0.008, T = 5.13）。G1母からG2母、G1母からG2父、G1父からG2父、のCAの世代間伝達の有無によってG3を分類した解析では、rGMVに有意な群間差のある領域は確認されなかった。 【結論】 以上の結果から、G3の視点では同程度のG2母の温かみや親密さであっても、それがG2母自身の父親(G1父)の高いCAを反映しているか、あるいはG1父の低いCAから翻って高くなったCAであるかによって、G3の脳発達への効果が異なる可能性が示唆された。養育態度の成り立ちの違いが子世代の発達の個体差に寄与する可能性に切り込んだ本研究は、親の被養育経験を考慮したペアレント・トレーニングの発展などに貢献すると期待できる。 | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-139
高い幸福健康度に関連する要因と血中分子の検討
Examination of factors and blood molecules related to health with high well-being
*稲田 祐奈(1)、東田 千尋(1)
1. 富山大学
*Yuna Inada(1), Chihiro Tohda(1)
1. University of Toyama
Keyword: health, well-being, daily activity, plasma
心身の健康に、幸福感の向上・維持を目標に加えたより水準の高い健康を“幸福健康”とし、幸福健康状態の維持・向上を可能とする方法を解明することを本研究は目指している。 ヒトの心身の健康には大きく分けて「余暇活動」と「社会的関係性」の2つの生活要因が関与しているとされている。2つの要因のうち、余暇活動は「認知」「身体」「社会」的要素に分類することができ、高齢者においては、「認知」「身体」「社会」的余暇活動が健康状態の改善要因であること、また3要素の活動をバランスよく行なうことが認知症発症リスクを軽減させることが示されており、心身の健康とライフスタイルは直結し、認知機能や身体機能もまた相互関係を有していると考えられる。我々は幸福健康状態には認知や感情・情動を司る脳と、筋肉などの末梢臓器の連関が良好であると考え、脳と末梢臓器の相互作用を担う分子が血液を介して循環して幸福健康状態に影響を与えているとの仮説を立てた。そこでメンタルヘルス(幸福度とQOL)、機能の健康状態（認知機能と身体機能）、日常的活動性（日常活動の実態調査と実際の活動量の測定）を定量し、幸福度が高く良い健康状態にある高齢者とそうでない高齢者を調べた。 研究参加者は日常生活に支障のない認知機能と身体機能を有する65歳以上の高齢者45名であった。メンタルヘルス評価を幸福感とQOL評価、認知機能評価をWAIS-IV知能検査、身体機能評価を筋力測定、歩行機能検査、日常的活動性評価をライフスタイル調査と加速度計計測によって実施した。血中分子の探索のため、血漿を採取した。全ての評価項目について相関分析を、採血により得られた血漿は網羅的プロテオミクス解析を行った。 メンタルヘルスと身体機能評価、日常的活動性評価と身体機能評価に相関が認められたため、さらに詳細な解析を行っている。血中分子については現在検討中である。本研究を進め、認知機能や身体機能が保たれ、かつ、メンタルヘルスが高いヒトに特徴的にみられる血漿中タンパク質を見出しそれらの機能を明らかにする。 | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-140
ヒト成人における脳の加齢様式と皮質微細構造
Brain aging mode and cortical microarchitecture in adult human
*佐々木 章宏(1,2)、Joonas A Autio(2)、Toshihiko Aso(2)、Hikaru Fukutomi(2)、Kyosuke Watanabe(2)、Kei Mizuno(1)、Yasuyoshi Watanabe(1)、Takuya Hayashi(2)
1. 理化学研究所 生命機能科学研究センター 健康病態科学研究チーム、2. 理化学研究所 生命機能科学研究センター 脳コネクトミクスイメージング研究チーム
*Akihiro Sasaki(1,2), Joonas A Autio(2), Toshihiko Aso(2), Hikaru Fukutomi(2), Kyosuke Watanabe(2), Kei Mizuno(1), Yasuyoshi Watanabe(1), Takuya Hayashi(2)
1. Lab. Pathophysiological and Health Sciences, RIKEN BDR, 2. Lab. Brain Connectomics Imaging, RIKEN BDR
Keyword: Aging in human, MRI, Diffusion, Structure
Brain aging is often associated with brain atrophy and declined cognitive functions in humans. However, less is known about how brain aging is associated with cortical microstructures. Here, we investigated the multiple variables of cortical microstructures including myelin and neurite in association with subject measures (SM) including age, affective and cognitive function in a modestly large sample of young to aged adult individuals. A total of 327 healthy individuals (18-79 years old, 161 females) were scanned structural MRI (sMRI) with T1-weighted (T1w) and T2-weighted (T2w), diffusion (dMRI) and resting-state functional MRI (rfMRI) with a 3T MRI scanner (MAGNETOME Prisma, Siemens, Erlangen, Germany). The SMs were collected from the majority of the subjects (N=286), who completed 17 questionnaires about demographics, affective state, and a cognitive function test battery (modified advanced trail making test). All brain images were analyzed with Human Connectome Project (HCP) minimal preprocessing pipeline. The sMRI was used to calculate cortical thickness, surface area and myelin contrast based on a ratio of T1w/T2w. The dMRI was used to calculate cortical neurite density (NDI), extra-neurite density (ExNDI) including glia, orientation dispersion (ODI) of neurite mapped on the cortical surface. The rfMRI data was denoised, mapped and registered across subjects on the cortical surfaces using an areal-feature-based registration method (MSMAll). Cortical metrics (CM) in both hemispheres were parcellated into 360 cortical areas using an HCP’s multimodal parcellation atlas. Association between multiple CMs and SMs was analyzed with a permutation-based canonical correlation analysis (CCA). We found that the primary mode (CCA1) exhibited a statistical significance in 358 among all the cortical parcels and the secondary mode (CCA2) in ten parcels. The loading of CCA1 for SMs highly correlated with age and the cognitive performances relevant to set-shifting, while not significantly correlated with affective states and fatigue index. The loading of CCA1 for CMs correlated with myelin and NDI and inversely correlated with ExNDI and cortical thickness. These findings indicate that the brain aging from young to middle aged individuals may involve cognitive changes, slimming of the glia related to the plasticity and condensing of myelin and neurite related to the stability of the cortical organization along life span. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-141
高次認知機能の発達をマウスで研究するための手法の確立
Establishment of methods to study the development of higher-order cognition in mice
*豊泉 英智(1,2)、下郡 智美(1)、岡ノ谷 一夫(2)、Thomas J McHugh(1)
1. 理化学研究所 脳神経科学研究センター、2. 東京大学大学院総合文化研究科
*Eichi Toyoizumi(1,2), Tomomi Shimogori(1), Kazuo Okanoya(2), Thomas J McHugh(1)
1. RIKEN Center for Brain Science, Saitama, Japan, 2. Grad Sch Arts and Sciences, Univ of Tokyo, Tokyo, Japan
Keyword: Higher-order cognition, Consciousness, In utero electroporation, Trace fear conditioning
Currently, studies of higher-order cognition and consciousness are in a chaotic state, with a lack of consensus in definition, methodology, theory, and physiological signature. I propose that studies focusing on the developmental aspect of cognition and consciousness, the “how it’s built”, will provide valuable insights into “how it works” of the higher-order cognition and to better interpret/organize the previous findings. In addition, the definition/theory-free nature of the “how it’s built” approach means that its application is not limited to consciousness, but it can be applied to related higher-order cognition in general. For the comprehensive and systematic survey of the developmental aspect of cognition, the animal model is the ideal option. However, to establish the “how it’s built” approach in rodents, there are a few missing parts. Namely, the gene-delivery method that allows neonatal transfection and the behavioral task that captures the development of complex cognition with established ontogeny.
I demonstrated that with newly developed trident-probe configuration, in utero electroporation, which has primarily been used for unilateral transfection in neurobiological studies, can be used to achieve prenatal bilateral focal strong persistent expression of genes. Bilateral transfections are demonstrated in the prelimbic cortex, anterior cingulate cortex, retrosplenial cortex, hippocampus, etc.
For a behavioral task that captures the development of complex cognition in mice, I focused on trace fear conditioning. This seemingly simple task that requires mice to associate the tone and the electric shock despite the 20s interval, employs PL, ACC, RSC, HPC, and EC in addition to all the structures necessary for regular delay fear conditioning. I established the ontogeny for trace fear conditioning in mice, with trace fear learning capacity emerging around P22~33.
In the future, I plan to combine manipulation of neural activity before birth, made possible by novel IUE configuration, and a cognitively demanding behavioral task with complete ontogeny, the trace fear conditioning. To elucidate the truly essential circuitry and physiology, as well as its critical periods for the development of higher-order cognition. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-142
コエンザイムQ10補充はマウス運動野における加齢性の神経活動低下を改善する
Coenzyme Q10 supplementations improve age-related decline of neuronal activities in the mouse motor cortex.
*井上 律子(1)、西宗 裕史(1,2)
1. 東京都健康長寿医療センター研究所 老化神経生物学研究室、2. 東京農工大学 大学院農学研究院
*Ritsuko Inoue(1), Hiroshi Nishimune(1,2)
1. Lab of Neurobiol of Aging, Tokyo Met Inst of Gerontology, Tokyo, Japan, 2. Dep of Applied Biol Sci, Tokyo Univ of Agriculture and Technology, Tokyo, Japan
Keyword: motor function, aging, plasticity, mitochondria
Motor function declines due to neurodegenerative diseases and physiological aging. We previously reported that the motor function and brain mitochondrial function improved concurrently in middle-aged mice treated with water-soluble nano-formula coenzyme Q10 (CoQ10) via drinking water for one week compared to age-matched controls. The movement was evaluated with a pole test, and the brain mitochondria were isolated to quantify the oxygen consumption rate using a high-resolution respirometry. However, the improved motor function was not due to the enhancement of muscle strength in middle-aged mice treated with CoQ10. In brain slices of middle-aged mice, we measured field excitatory postsynaptic potentials (fEPSPs) in the motor cortex. We found that the fEPSP amplitudes were significantly smaller in the primary motor area of middle-aged mice compared to young mice suggesting an age-related decline of neuronal activities. Interestingly, fEPSP amplitudes reverted to the young mice level in brain slices prepared from middle-aged mice treated with the CoQ10 for one week. These results suggested that the improved synaptic transmission efficiency of the primary motor area may underlie the motor function improvement by the CoQ 10 supplementation.
We hypothesized that the CoQ10 directly affected synaptic transmission efficiency and examined the effects of acutely administered CoQ10 on brain slices of middle-aged mice to seek the mechanism of motor function improvement. However, the acute CoQ10 administration did not enhance the fEPSP amplitudes in the primary motor area of slices prepared from middle-aged mice. Interestingly, the acute CoQ10 treatment with high-frequency stimulation induced long-term potentiation (LTP) of the primary motor area of slices prepared from middle-aged mice. Notably, fEPSP amplitude in the primary motor area of these slices showed larger input-output relationships after the LTP expression compared to before the high-frequency stimulation. These data suggest that the CoQ 10 supplementation potentially enhances synaptic plasticity efficacy, resulting in improved basal fEPSP level in the motor cortex of middle-aged mice. The mechanism of motor function improvement in middle-aged mice by the CoQ10 supplementation appears to be due to restorations of the brain mitochondrial function and the basal neuronal activities in the motor cortex. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-143
RP58減少を伴う早期老化に対する治療戦略
A tetracycline antibiotic minocycline prevents early aging phenotypes of heterozygous for RP58
*田中 智子(1)、平井 志伸(1)、眞部 寛之(2)、遠藤 堅太郎(1)、新保 裕子(1)、岡戸 晴生(1)、吉種 光(1)
1. 東京都医学総合研究所、2. 同志社大学
*Tomoko Tanaka(1), Shinobu Hirai(1), Hiroyuki Manabe(2), Kentaro Endo(1), Hiroko Shinbo(1), Haruo Okado(1), Hikari Yoshitane(1)
1. Tokyo Metropolitan Institute of Medical Science, 2. Doshisha University
Keyword: Aging
In humans, cognitive and motor function develop in association with maturation, followed by decline in advancing age. Recently, medical technology is advancing rapidly, and therefore life-span is getting longer. In this study, we aimed to provide a method for extending healthy life-span by preventing age-related phenomena. To this end, we focused on a transcriptional repressor RP58, whose expression level is decreased during aging in the human cortex. In the Rp58 hetero-KO mice, the object location memory was impaired even at 4-5 months, while it was normal in wild-type mice at 4-5 months but was impaired at 12-18 months, indicating an early onset of the impaired spatial memory in the Rp58 hetero-KO mice. We clarified that the impairment was due to a defect in learning the place of object rather than in recalling the memory. As the underlying mechanism, the Rp58 hetero-KO mice showed early onsets of DNA damages accumulation and microglial activation in dentate gyrus during aging due to a defect in the DNA repair. To ensure an availability of the Rp58 hetero-KO mice as the human-like early aging model, we focused on a function of mitochondria, and identified the mitochondrial abnormalities in the Rp58 hetero-KO mice at 4-5 months. These results consolidate that RP58 is involved in inflammation and DNA damage repair, and these disabilities lead to impairment of cognitive function. Impressively, continuous treatments of minocycline, which has neuroprotective and anti-inflammatory effects, prevented the facilitation of age-related phenomena in the Rp58 hetero-KO mice. Our research indicates the availability of the Rp58 hetero-KO mice as novel human-like early aging model and provides the therapeutic strategy for age-related phenomena by using minocycline (Tanaka et al., 2021). | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-144
局所脳血流変化が及ぼす神経活動と行動への影響について
Neural activity and behavioral impacts of alterations in regional cerebral blood flow
*阿部 欣史(1)
1. 慶應義塾大学医学部
*Yoshifumi Abe(1)
1. Keio University School of Medicine
Keyword: cerebral blood flow, optogenetics, neural activity, locomotion
How the brain regulates its blood supply and how cerebral blood flow (CBF) controls brain function are pivotal questions in both basic and clinical neuroscience research. To approach this question, we generated vascular optogenetics resources in which smooth muscle cells and endothelial cells expressed optical actuators in the brain. An illumination upon channelrhodopsin-2 (ChR2)-expressing mice induced a local CBF reduction. Photoactivated adenylyl cyclase (PAC) is an optical probe to increase intracellular cyclic adenosine monophosphate (cAMP) and an illumination upon PAC-expressing mice induced a local CBF increase. We targeted the ventral striatum, determined the temporal kinetics of CBF change, and optimized the illumination intensity to confine the effect in the ventral striatum. We investigated the effects of local CBF changes on neural activity and locomotion behavior. As a result, local CBF reduction decreased neural activity while local CBF increase did not change it. The local CBF reduction at the ventral striatum induced a decrease in mouse locomotion. In this study, we successfully demonstrated that local CBF alterations manipulated by the vascular optogenetics affected neural activity and mouse behavior. Vascular optogenetic animal resources will accelerate the research linking among vasculature, circuit, and behavior in health and disease. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-145
キイロショウジョウバエにおける乳酸菌SBT2227株の睡眠促進効果の神経遺伝学的解析
Molecular and neural factors mediating sleep-promoting effects of lactic acid bacteria strain SBT2227 in Drosophila melanogaster
*石元 広志(1)、上川内 あづさ(2)
1. 名古屋大学理学研究科附属ニューロサイエンス研究センター、2. 名古屋大学理学研究科生命理学
*Hiroshi Ishimoto(1), Azusa Kamikouchi(2)
1. Neuroscience Institute, Grad Sch Sci, Nagoya Univ, Japan , 2. Div Bio Sci, Grad Sch Sci, Nagoya Univ, Japan
Keyword: Lactic acid bacteria, Sleep, Drosophila, Lactobacillus
Lactic acid bacteria (LAB) influence multiple aspects of host brain function. We recently identified a LAB strain (Lactobacillus plantarum SBT2227) that promotes sleep in Drosophila, however as in many other cases in the host brain action of LABs, it is still an open question what group of molecules and neurons are responsible for this sleep effect. Here, we report putative responsible neurons for the sleep effect of SBT2227. Administration of SBT2227 primarily increased the amount of sleep and decreased sleep latency at the beginning of night-time. Using this sleep phenotype as an indicator, we screened a group of neurons required for the effect of SBT2227 by target neuron-specific molecular manipulation using the Gal4/UAS system. As the result, a group of neurons comprising the central complex was found to be the putative responsible neurons. These neurons are also known to play a central role in the regulation of sleep in Drosophila. In addition, we identified genes that are essential for the sleep effects of SBT2227 in these neurons. The molecular and neuronal factors mediating sleep effects of SBT2227 will provide new insights into the interaction between the brain and gut bacteria. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-146
The anatomical study of the superior colliculus to inferior olive pathway.
*Deviana David(1)
1. Okinawa Institute of Science and Technology
Keyword: Superior Colliculus, Anatomical study, Inferior Olive
The superior colliculus (SC) and inferior olive (IO) are two evolutionarily conserved regions important for animal survival. Previous studies have proposed a role for SC in defensive behaviors and orientation while IO is a part of the olivo-cerebellar system (OCS) which mediates well-coordinated movement with precise timing. While previous studies have shown the existence of neuronal projection from the SC to the IO in mice, there has been no further investigation on the morphological and functional properties of the pathway. The current study aims to describe the structural and morphological properties of the SC-IO pathway in mice. Anterograde and retrograde viral labelling of the pathway was used to generate a projection map between SC and IO. Furthermore, sparse labelling of IO neurons allowed sub-cellular localization and morphological examination of the virally-labeled SC axon termination zones.
The data from anterograde labeling suggests a topographical projection from lateral and medial part of SC to the IO. The IO projecting neurons from the lateral SC were found originating from both superficial and deep layers. However, the projections from the medial part of the SC were only found originating from the superficial layer.
In conclusion, the current results are able to differentiate the IO-projecting and non-IO projecting SC neurons. The results also suggest a possibility that different parts of the SC send projections to different parts of the IO. However, further experiments and replications are required for more complete description. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-147
スナネズミにおける超音波発声の周波数変調メカニズム
Frequency modulation mechanism of ultrasonic vocalization in Mongolian gerbils (Meriones unguiculatus).
*西堀 諒(1)、田中 一樹(1)、小林 耕太(1)
1. 同志社大学大学院生命医科学研究科
*Ryo Nishibori(1), Kazuki Tanaka(1), Kohta I Kobayasi(1)
1. Grad Sch Life and Medical Sciences, Univ of Doshisha, Kyoto, Japan
Keyword: ultrasonic vocalizations (USVs), social communication, anatomy, Mongolian gerbil
Many species of rodent produce ultrasonic vocalizations (USVs) for social communication. USVs are observed in various behavioral contexts, predominantly in infant-mother interaction, aggression, and mating behavior, and its spectral temporal structure, especially frequency modulation, varies systematically across the contexts. However, sound production mechanism remains largely unclear. In this study, we focused on gerbils (Meriones unguiculatus), which often communicate by vocalization, and investigated the mechanism of frequency modulation (FM) in USVs. Deceased gerbil had a needle inserted into its trachea. Air of various pressures was pumped into the trachea and produced sounds were recorded. As a result, steady air flow produced ultrasonic sound comparable to their USVs and frequency of the sound increased with increasing air pressure. Altering the tension of the vocal cords generated rapid frequency modulation. When gerbils meet other individuals, they often emit short USV named “greeting call”, which is characterized by an upward FM of about 5 kHz. In addition, while mating they produced long USVs (mating call), which is characterized by a series of rapid modulations of about 5 kHz over slow entire FM. Our result suggests that FM of greeting call could be produced mainly by changing flow rate of air from lungs, while FM of mating call could be produced by changing the tension of vocal cords simultaneously with air flow rate. Currently, we are planning to conduct similar experiments using gerbil pups. In the early postnatal period, gerbils produce USVs with complex frequency modulation similar to the mating call. These investigations will help us to elucidate development of vocalizations. In addition, it could serve as a basis for research on the neural development of vocalizations. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-148
胎仔期のネオニコチノイド暴露が成熟後のマウス脳機能に与える影響
Effects of prenatal exposure of mice to neonicotinoid pesticides on the brain functions in the adult stage
*大西 浩史(1)、森谷 晃(1)、大谷 修平(1)、権 ダニエル(1)、森田 紋子(1)、浦野 江里子(1)、橋本 美穂(2)、関島 恒夫(3)
1. 群馬大学大学院保健学研究科、2. 九州保健福祉大学薬学部、3. 新潟大学農学部
*Hiroshi Ohnishi(1), Akira Moriya(1), Shuhei Ohtani(1), Daniel Gon(1), Ayako Morita(1), Eriko Urano(1), Miho Sato-Hashimoto(2), Tsuneo Sekijima(3)
1. Gunma Univ Grad Sch Health Sci, Gunma, Japan, 2. Sch Pharm Sci, Kyushu Univ Health Welfare, Miyazaki, Japan , 3. Fac Agriculture, Niigata Univ, Niigata, Japan
Keyword: neonicotinoid, pesticide, behavior
Neonicotinoid pesticides are agonists of the nicotinic acetylcholine receptor (nAChR) and has a strong and selective insecticidal effect by acting specifically on the insect nAChR. Neonicotinoid pesticides are thought to be less toxic to vertebrates and is now widely used as a pesticide. Recently, it has been reported that neonicotinoid pesticides also affect non-target insects and may have adverse effects on the environment, such as bee-colony collapse disorder and reduction of insect-eating birds. In addition, there are concerns about their direct effects on the mammals inhabiting the farm, and humans may also be affected by neonicotinoid pesticides due to aspiration of pesticide spray and ingestion of pesticide residual food. In this study, we investigated the effect of prenatal exposure of mice to clothianidin (CLO), a member of the neonicotinoid pesticides, on the brain function in the post-developmental adult stage. Fetal C57BL/6N mice were exposed to CLO by supplying pregnant mother mice with drinking water containing CLO. To limit the effects of CLO-exposure to the fetal period, newborn mice were separated from their mother immediately after birth and housed with a postpartum female ICR mice as “nanny” that have not been exposed to CLO. As a control, newborn mice from CLO-unexposed mother mice were also separated from their mother and housed with normal nanny ICR. When these mice have been mature adults, we evaluated their brain function by behavioral analysis. After the behavioral analysis, brain samples were collected from these animals and used for histochemical study and transcriptome analysis. CLO-exposed mice grew normally without any obvious abnormalities and exhibited normal locomotor activity. On the other hand, CLO-exposed mice exhibited significantly impaired memory formation as assessed by the contextual fear conditioning test. Although no structural abnormalities were found in the brain of CLO-exposed mice by histochemical analysis, we found several genes that altered expression property in the hippocampus of CLO-exposed mice. Our results suggest that prenatal exposure of mice to CLO seems not to have obvious effect on the development of the mammalian brain structures, but may have long-lasting impact on the higher brain functions in the adult stage. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-149
Changes in the gut microbiome associated with domestication of mice
*Bhim B. Biswa(1,2), Hiroshi Mori(1,3), Atsushi Toyoda(4), Ken Kurokawa(1,5), Tsuyoshi Koide(1,2)
1. The Graduate University of Advanced Studies, SOKENDAI, Mishima, Shizuoka, Japan, 2. Mouse Genomics Resource Laboratory, National Institute of Genetics, Mishima, Shizuoka, Japan, 3. Genome Diversity Laboratory, National Institute of Genetics, Mishima, Shizuoka, Japan, 4. Comparative Genomics Laboratory, National Institute of Genetics, Mishima, Shizuoka, Japan, 5. Genome Evolution Laboratory, National Institute of Genetics, Mishima, Shizuoka, Japan
Keyword: Tameness, Microbiome, Domestication, Mice
Domestication is a sustained multi-generational process in which animals are tamed and kept as livestock or pets. With an increasing demand for new food sources, rapid domestication of wild animals is considered a viable option. However, the conventional method of domestication, ie, Several studies have recently identified links between the gut microbiome and tameness in mice. Therefore, in We used wild heterogeneous stock (WHS) mice, the present study, we tried to reveal the association between the gut microbiome and tameness in mice. Which were developed from eight wild strains of mice by selectively breeding for active tameness over many generations, resulting in two tame and two control groups.
[Methods] Two selected and two control groups were used from the 27th generation of WHS mice. Ten males and ten females from each group were tested for active tameness and subjected to faeces collection. Metagenomic DNAs were extracted from each animal faeces, followed by shotgun Bioinformatics analysis is done on the sequences obtained to conduct taxonomic and functional analysis of the gut microbiome. Blood plasma was also collected from the same mice for metabolomic analysis.
[Results] We found significantly higher levels of active tameness in selected groups than in control groups. Taxonomic analysis of mouse gut microbiome reveals that all four groups have similar gut microbiota composition, with few microbiome species having statistically significant differential abundance between control and selected mice After doing functional analysis of the sequences obtained, we found six metabolic pathways in the gut microbiome, which are differentially abundant between control and selected mice at the significant level. Of these pathways, four are amino acid degradation pathways, and two are fatty acid synthesis pathways. Metabolic by-products of these pathways might have a role in changing the host's behaviours, specifically tameness in the present work. Currently, we are conducting metabolomic analysis of the mice blood plasma to identify these metabolic by-products. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-150
Effect of Estrogen receptor α (ERα) gene polymorphisms in maternal behavior in mice
*Lalithadevi Mallarapu(1,2), Keiko Takanami(1,2), Akira Tanave(3), Yuji Imai(1), Tsuyoshi Koide(1,2)
1. Mouse Genomics Resource Laboratory (MGRL), National Institute of Genetics (NIG), Mishima, JAPAN, 2. Department of Genetics, Graduate University of Advanced Studies (SOKENDAI), Mishima, JAPAN, 3. Laboratory for Mouse Genetic Engineering, RIKEN Quantitative Biology Center, Osaka, JAPAN
Keyword: Estrogen Receptor, Polymorphisms, Maternal behavior, Mice
Maternal behaviors are important for survival of offspring. Previous studies implicated that gene polymorphisms play an important role in determining maternal responsiveness, but details of the neural mechanism remain elusive. Here, we addressed how polymorphisms in ERα, which is encoded by Esr1 gene, can affect maternal behavior in mice. Our study identified that mice from different genetic background, i.e. laboratory strain C57BL/6J (B6) and wild derived strain MSM/Ms (MSM) differ in Esr1 gene structure. A coding polymorphism (9bp) was identified in exonic region of Esr1 gene in MSM when compared to B6. To analyse the role of the “9bp coding polymorphism”, we developed an Esr1Δ9 mice in which the “9bp” sequence was deleted in B6 mice through CRISPR/Cas9-mediated genome editing. Interestingly, mice with heterozygous deletion of “9bp” (Esr1+/Δ9) showed more severe phenotype than homozygous deletion (Esr1Δ9). The low pup survival rate and abnormal maternal behavior (reluctant to retrieve pups) was observed in Esr1+/Δ9 mice. Immuno-histochemical analysis of medial preoptic area (MPOA) of brain, showed lower number of ERα (MPOAERα +) positive cells. As MPOAERα +cells are the key mediators of pup approach and retrieval, abnormal maternal behavior of Esr1+/Δ9 mice is related to lower number of MPOAERα + cells. The decrease in ERα was attributed with rapid degradation caused by structural instability of ERα. However, extensive analysis of ERα structural stability is needed to address rapid degradation. Altogether, this is the first study to report how ERα genetic polymorphism affect maternal behavior in mice. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-151
サイトカインレベル、前部帯状回ネットワークオシレーション並びに認知行動に対し全身性炎症が与える影響
The effects of inflammation on cytokines, network oscillation in the anterior cingulate cortex, and cognitive behavior.
*平尾 鮎美(1)、北條 泰嗣(1)、村上 元(2)、伊藤 吏那(1)、橋爪 幹(1)、村越 隆之(1)、魚住 尚紀(1)
1. 埼玉医科大学医学部生化学、2. 埼玉医科大学医学部教養教育
*Ayumi Hirao(1), Yasushi Hojo(1), Gen Murakami(2), Rina Ito(1), Miki Hashizume(1), Takayuki Murakoshi(1), Naonori Uozumi(1)
1. Department of Biochem, Faculty of Medicine, Saitama Medical Univ, Iruma, Japan, 2. Department of Liberal Arts, Faculty of Medicine, Saitama Medical Univ, Iruma, Japan
Keyword: Anterior cingulate cortex, Network oscillation, Inflammatory cytokines, Novel object recognition
Network oscillation generated by neural circuits in the anterior cingulate cortex (ACC), plays an important role in the integration of higher functions including cognition, emotion and attention. Because systemic inflammation causes cognitive impairment, it is expected that inflammatory cytokines may alter ACC network oscillations. Therefore, we investigated the effects of inflammatory cytokines on ACC-related task and kainic acid (KA) -induced network oscillations in an ACC slice. Our final goal is to establish the relationship between LPS-induced elevation of cytokine level and the profiles of behavior and network oscillations. Male C57BL/6J mice were intraperitoneally administered with 30µg/kg of lipopolysaccharide (LPS). Three hours after administration, novel object recognition test (NOR) was performed, and followed by preparation of blood sample for IL-6 quantification and brain slices containing ACC for electrophysiology. To examine the effects of LPS administration on cytokines induction, quantification of IL-6 in serum and in the ACC were performed. LPS treatment significantly increased serum IL-6 level and tended to increase brain tissue IL-6 level. Field potential was recorded extracellularly from three points within the ACC, the superficial (Sp1, Sp2) and deep (Dp1) layers of Cg1. The network oscillation was evoked in two ways: perfused KA alone and KA+ histamine. Power spectrum density (PSD) was calculated by fast Fourier transformation and the area under the curve within the following range was used as an index of oscillation power: theta (3-8 Hz), alpha (8-12 Hz), beta (12-30 Hz), low gamma (30-50 Hz), high gamma (50-80 Hz), and total (3-80 Hz). Two-way ANOVA test revealed the main effect of LPS or histamine, and their interaction on network oscillation only at Sp2, but neither Sp1 nor Dp. Hence, we further analyzed the oscillation power of each frequency range components in Sp2 using multiple comparisons. The power of KA-induced network oscillation significantly increased in the LPS group as compared with the control group. Histamine enhanced the power of KA-induced network oscillations in control group, however this enhancement effect was not observed in the LPS group, supporting the interaction effect (LPS × histamine). In the NOR, the exploration time for a novel object decreased in LPS group, although there was no significant difference in the index of novel object recognition between the control and LPS groups. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-152
洞察問題解決中のあたため期における脳機能ネットワークの分析
Functional Brain Networks Analysis During Incubation Phase of Insight Problem-solving
*大隈 玲志(1)、栗原 勇人(1)、髙橋 徹(1)、大須 理英子(1)
1. 早稲田大学
*Reiji Ohkuma(1), Yuto Kurihara(1), Toru Takahashi(1), Rieko Osu(1)
1. Waseda University
Keyword: Insight problem-solving, fNIRS, Functional Connectivity, Wavelet Phase Coherence
Incubation, the unconscious processing of problems, is important for insight problem solving with inspiration. During incubation, it is known that problem-solving gradually progresses through relaxation of constraints. Previous researches has shown that throughout the incubation, multiple functional brain networks such as the default mode network (DMN) and working memory network (WMN) are activated. However, it is not known how the functional connectivity at the start of incubation (start of insight) differs from that at the end of incubation (just before Aha). In this study, we measured brain activity during insight problem solving with functional near-infrared spectroscopy (fNIRS) and compared functional connectivity at the beginning and end of the incubation in all channels. Thirty-one subjects (18 males, 13 females, 21.5±1.14 years old) took part in the experiment. The insight problem was a slot machine task of predicting numbers based on past information, which is developed by Terai (2005). We used fNIRS (34channels) instrument to measure changes in oxyhemoglobin concentration. As a functional connectivity measure, we used wavelet phase coherence (WPCO), which can calculate the connectivity in different regions independent of amplitude. To check the consistency of the WPCO, 100 surrogate signals were created using the Amplitude Adjusted Fourier Transform (AAFT) method, which creates surrogate signals without changing the data distribution and power spectrum, and the values of the coherence coefficients were verified. If the WPCO of the original signal is higher than the sum of the mean and twice the SD of the surrogate WPCO, then the value of the WPCO was valid. The test was a within-subjects paired sample t-test of WPCO at the beginning of insight and just before Aha. Fifteen of them answered the insight questions correctly. The result of the analysis showed that the functional connectivity between the right prefrontal cortex (right PFC) and the right inferior temporal gyrus (right ITG), the right orbitofrontal cortex (right OFC) and the right dorsolateral prefrontal cortex (right DLPFC), and the right orbitofrontal cortex (right OFC) and the left middle temporal gyrus (left MTG) decreased as the incubation proceeded in the solvers. In addition, the functional connectivity of the left prefrontal cortex (left PFC) and right angular gyrus (right AG) increased. The results suggest that the functional coupling of the incubation period varies with phase. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-153
鳴禽類における歌の種分化の神経分子メカニズム
Neural molecular mechanisms of the song speciation in songbirds
*田路 矩之(1)、柴田 ゆき野(2)、辰本 将司(3)、石川 裕恵(3)、郷 康広(3,4,5)、和多 和宏(1,2)
1. 北海道大学大学院理学研究院、2. 北海道大学大学院生命科学院、3. 自然科学研究機構生命創成探究センター、4. 自然科学研究機構生理学研究所、5. 総合研究大学院大学生命科学研究科
*Noriyuki Toji(1), Yukino Shibata(2), Shoji Tatsumoto(3), Hiroe Ishikawa(3), Yasuhiro Go(3,4,5), Kazuhiro Wada(1,2)
1. Dept of Sci, Hokkaido Univ, Hokkaido, Japan, 2. Grad Sch life Sci, Hokkaido Univ, Hokkaido, Japan, 3. ExCELLS, NINS, Aichi, Japan, 4. NIPS, NINS, Aichi, Japan, 5. Sch Life Sci, SOKENDAI, Kanagawa, Japan
Keyword: Species-specific behavior, Songbird, Single cell RNA-seq, Speciation
The evolution of species-specific behaviors in animals has been considered to associate with physiological and anatomical speciation of neural circuits. However, due to the absence of appropriate animal models, the speciation process of neural circuits at molecular and cellular levels has remained largely unknown. Songbirds generate species-specific songs with a neural circuit called the song system, whose structure is well conserved among songbirds. In addition, songbirds have individual differences in their songs due to the variation in the genetic background within the species. Thus, we attempted to elucidate the molecular and cellular mechanisms of behavioral phenotypic speciation by using songbirds, which have both “neural circuits directly related to behavioral phenotypes” and “specific phenotypes inter- and intra-species“. In this study, we examined two neuronal nuclei (HVC and RA) composing the vocal motor pathway of the song systems in three songbird species (Taeniopygia guttata, T. bichenovii, and Neochmia modesta). Single-cell RNA sequencing analysis was performed for HVC and RA to analyze transcriptomic differences between species and individuals. In the interspecies comparison, we validated the gene expression patterns for each neural and non-neural cell type and found more significant species differences in gene expression patterns in excitatory projection neurons in both HVC and RA compared to other cell types. Gene ontology analysis showed that the differentially expressed genes in excitatory projection neurons were selectively accumulated in ion channels and neuronal receptors. In addition, intra-species comparisons similarly revealed individual differences in gene expression patterns specific to excitatory projection neurons. These results suggest that speciation in the neural functional properties of excitatory projection neurons could be a driving factor for the evolution of the species-specific songs in songbirds. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-154
キイロショウジョウバエの睡眠を調節する二つの神経伝達モード
Drosophila sleep regulated by a neuronal function with dual neurotransmission modes
*伊藤 悠一郎(1)、上川内 あずさ(1)、石元 広志(1)
1. 名古屋大学大学院理学研究科
*Yuichiro Ito(1), Azusa Kamikouchi(1), Hiroshi Ishimoto(1)
1. Grad Sch Sci, Univ of Nagoya, Aichi, Japan
Keyword: Sleep, Drosophila melanogaster, dual neurotransmission, innexin
Animals exhibit sleep and sleep-like behaviors, and daily sleep amount varies depending on species. This suggests the involvement of genetic factors for the controlling sleep amount. However, the mechanism of what molecules regulate the functioning of neural circuits to define the amount of sleep has not yet been fully elucidated. To address this question, we focused on a group of inter-neurons (Lkr neurons) potentially modulating the activity of a sleep promoting center in the insect brain; fan-shaped body (FB) in Drosophila melanogaster. Sleep amount was significantly decreased by inhibition of the Lkr neuronal activity by expressing an inwardly rectifying potassium channel (Kir2.1) using Drosophila binary expression system (Gal4/UAS system). This suggests that the Lkr neurons positively regulate the sleep amount. Kir2.1 thought to suppress an electrical activity of target neurons, and thus is thought to inhibit information flow via synaptic transmission, both of chemical and electrical synapses. To suppress chemical synapses specifically, tetanus toxin light chains (TeNT) was expressed in Lkr neurons. Contrary to our expectation, flies expressing TeNT increased the sleep amount. This result was the exact opposite from the flies expressing Kir2.1. What are the causes of such contradiction? We hypothesized that electrical synapses may contribute to these phenomena. To examine this idea, we knocked-down innexin genes in Lkr neurons and checked the sleep phenotype. As a result, suppression of one type of innexin gene expression reproduced the sleep phenotype of flies expressing Kir2.1. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-155
Sleep alterations by dietary regulations in a Drosophila dopamine transporter mutant
*Rabia Garibagaoglu(1), Riho Kobayashi(1), Hiroyuki Nakagawa(1), Jun Tomita(1), Kazuhiko Kume(1)
1. Department of Neuropharmacology, Grad Sch of Pharm Sci, Nagoya City Univ, Nagoya, Japan
Keyword: dopamine, fumin, drosophila, sleep
Dietary restriction extends the lifespan of numerous species including fruit flies, Drosophila melanogaster. It is an established model for examining longevity and sleep. The Drosophila activity monitoring system is being used for the measurements. Sleep and locomotor activity are affected by dietary regulations. Studies have shown that the dopamine transporter mutant, fumin, has more obvious changes in sleep than wild type and considered that the dopamine levels play a role in it (Yamazaki et al., Biochem. Biophys. Res. Commun., 2012). However, the molecular mechanism of how dopamine connects diet and sleep is not well understood which is what was focused on this study. Initially, for sleep analysis of fumin, we examined the effect of different concentrations of food using 1, 5, 10 and 15% sucrose-yeast (SY), and 5% sucrose food at 25°C under a 12/12 light-dark cycle. Sleep bouts were defined as no activity for more than 5 minutes. There was a significant decline in the locomotor activity in 1% SY and 5% sucrose food compared to higher concentrations. To explore the dopaminergic pathway, amino acids that are involved in the formation of dopamine, which are l-DOPA (l-3,4-dihydroxyphenylalanine), l-phenylalanine and l-tyrosine, were added to the food separately. The results showed that there was a significant change in the activity pattern with l-DOPA in 5% sucrose food but not in 1% SY. There were no changes observed in l-phenylalanine and l-tyrosine. Further, we are investigating the effect of amino acids on sleep in this phenotype. Initial results from the analysis of dietary conditions will be presented and the effects of amino acids will be discussed. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-156
Paradoxical Sleep in Octopus laqueus
*Aditi Pophale(1), Kazumichi Shimizu(1), Teresa Iglesias (1), Samuel Reiter(1)
1. Okinawa Institute of Science and Technology, Okinawa, Japan
Keyword: Sleep, REM sleep, cephalopods, neuroethology
A holistic understanding of the behavioural and neural phenomenon of sleep continues to elude modern science. Behaviorally, there are four “criteria” that are used to distinguish sleep from other states. These are: quiescence, rapid reversibility (waking up), decreased arousal to stimulation and homeostatic regulation. Neurally, sleep can be divided into at least two distinct stages, Non-Rapid Eye Movement (NREM) characterized by slow, synchrounous brain activity and periodic bouts of Rapid Eye Movement (REM) sleep characterized by fast, asynchrounous brain activity. All animals examined show behavioral sleep however, only vertebrates have demonstrated two distinct neural stages of sleep. We decided to study sleep in octopuses, unique among invertebrates for the neural control of their skin patterns and color. Octopuses can change the color of their skin using ink sacs, called chromatophores, that are under neuro-muscular control. Precise quantification of the skin patterns they produce can provide a rich “readout” of the animal’s perceptual state (Reiter et al., 2018). We recorded octopus (Octopus laqueus) resting behavior in laboratory settings continuously over days. To quantify the changes in their skin color, we trained deep neural networks (Mask R-CNN) to detect the octopus and calculated intensity of the pixels. We observed that Octopus laqueus lies relatively still and adopts a white color and a smooth texture, and a flat posture during rest. Every ~45 minutes its entire body rapidly cycles through a range of patterns and textures for a several minutes after which it turns white again. We found that this phenomenon fulfills the behavioral criteria for sleep. We are currently conducting experiments to measure the electrophysiological correlates of these states. We are collecting high resolution video of these active sleep episodes to understand their dynamics over time and across individuals. Studying sleep in cephalopods because of their evolutionary history and unique skin, can integrate insights from comparative ethology and neuroscience. This synthesis can provide a better understanding of the “core” functions of sleep. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-157
海馬による感覚入力の分類と反響統合
The hippocampus as a sorter and reverberatory integrator of sensory inputs
*野本 真順(1)、村山 絵美(1)、大野 俊太郎(1)、鈴木（大久保） 玲子(1)、井ノ口 馨(1)
1. 富山大学
*Masanori Nomoto(1), Emi Murayama(1), Shuntaro Ohno(1), Reiko Okubo-Suzuki(1), Kaoru Inokuchi(1)
1. University of Toyama
Keyword: Hippocampus, Recurrent circuit, Reverberatory activity, Memory association
The hippocampus must be capable of sorting and integrating multiple sensory inputs separately but simultaneously. There are two parallel pathways, the trisynaptic pathway important for one-trial contextual learning and the monosynaptic pathway important for temporal association. Among these pathways, the CA3 has a unique system, a recurrent circuit forming extensive interconnections within CA3 cells. During sensory inputs in fear learning, the entorhinal-hippocampal inhibitory mechanism restricts incorporation of unconditioned stimulus (US) input as a part of conditioned stimulus (CS) representation in the hippocampus. On the other hand, aversive stimulus propagates into the hippocampus and activates hippocampal neurons. These findings implies a novel hippocampal function in which CS and US association occurs after the termination of sensory inputs. However, it remains to be elucidated how the hippocampus executes two distinct processes, sorting and integrating the CS and US inputs during memory encoding. Theoretical models have suggested that the CA3 recurrent circuit implemented with N-methyl-D-aspartate receptor (NR) function has a potential to generate reverberatory neuronal activities without input from external stimuli, and acts as an associator of temporally separated episodes by filling a temporal gap between discontinuous events. We hypothesized that, in the delayed conditioning in which the US is simultaneously paired with the preceding CS, the hippocampal network is programmed to process sensory information after termination of sensory inputs and reverberatory activities, which could repeat the CS and the US representations, serve as an integrator to link neutral and aversive stimuli. We sought to determine whether and how reverberatory activities contribute to the CS-US association during conditioned learning.
Here we demonstrate that in mice, synchrony between conditioned stimulus (CS) and unconditioned stimulus (US)-responsible cells occurs during the reverberatory phase, lasting for approximately 15 s, but not during CS and US inputs, in the CA1 and the reverberation is crucial for the linking of CS and US in the encoding of delay-type cued-fear memory. Retrieval-responsive cells developed primarily during the reverberatory phase. Mutant mice lacking NRs in CA3 showed a cued-fear memory impairment and a decrease in synchronized reverberatory activities between CS- and US-responsive CA1 cells. Optogenetic CA3 silencing at the reverberatory phase during learning impaired cued-fear memory. Our findings suggest that reverberation recruits future retrieval-responsive cells via synchrony between CS- and US-responsive cells. The hippocampus uses reverberatory activity to link CS and US inputs, and avoid crosstalk during sensory inputs. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-158
新規次元削減手法iSeqは、内側前頭前皮質の高次機能が、単純な機能の組み合わせにより実現されていることを明らかにする
A novel dimensionality reduction method, iSeq, reveals that higher-order functions of medial prefrontal cortex are represented as a combination of simpler functions
*大野 駿太郎(1,2)、野本 真順(1,2)、井ノ口 馨(1,2)
1. 富山大学医学薬学研究部生化学講座、2. 富山大学アイドリング脳科学研究センター
*Shuntaro Ohno(1,2), Masanori Nomoto(1,2), Kaoru Inokuchi(1,2)
1. Department of Biochemistry, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2. Research Center for Idling Brain Science, University of Toyama, Toyama, Japan
Keyword: dimensionality reduction, prefrontal cortex, rule learning, neuronal sequence
Although the medial prefrontal cortex (mPFC) plays an important role in rule learning and decision making, it is still unclear how these functions are represented in the mPFC. Related to this, many literatures have shown that the dynamics of neurons associated with behavior or cognition tend to have a sequential structure. However, since the functions of mPFC are of a higher-order, it is unlikely that these are represented as a single sequence.
We hypothesized that the functions of mPFC is represented by multiple sequential elements. In other words, the complex neuronal activity in the mPFC can be viewed as a combination of neuronal sequential activities, each of which encodes simple behavior and cognition. To detect them, we have developed a novel dimensionality reduction method called iSeq. iSeq, an improvement of convNMF[1], automatically extracts a statistically valid number of sequential activities from a time series of hundreds of neuronal activities.
To investigate the neuronal activity of the mPFC in animals learning rules on their own, we trained mice to perform a Y-maze task over 6 days, during which their mPFC was recorded by calcium imaging. Analysis of this data with iSeq revealed that the mPFC during the task contains neuronal sequences which express strategic behavior and response to or prediction of reward. The activity patterns of these neuronal sequences were distinctly different during successful and unsuccessful tasks, and conversely, the chronological variation in the intensity of the neuronal sequences could be used to predict the success or failure of subsequent tasks. In addition, by adding null cells to the data prior to sequence detection, groups of neurons that are significantly more active than null cells can be identified as the representative neurons for each sequence, making it possible to compare sequences with each other in terms of population and order. This comparison showed that neuronal sequences of mPFC remained consistent across days.
Analysis with iSeq revealed that in the mPFC, the higher-order function of rule learning is decomposed into units such as behavior and reward, each of which is represented in the form of neuronal sequences. And this approach of using iSeq to automatically extract intercomparable neuronal sequences is expected to be applicable to and effective for all brain regions in general.
[1] Smaragdis. IEEE/ACM Trans Audio Speech Lang Process., 15:1-12, 2007 | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-159
REM sleep inspires cognitive inference in cortical networks
*Kareem Mahmoud Abdou(1), Kiriko Choko(1), Mohamed H. Aly(1), Reiko Okubo-Suzuki(1), Ahmed Zaher(1), Shin-ichi Muramatsu(2), Kaoru Inokuchi(1)
1. Department of Biochemistry, Grad Sch of Med, Univ of Toyama, Toyama, Japan, 2. Institute of Medical Science, The Univ of Tokyo, Tokyo 1088639, Japan
Keyword: Inference, Sleep, Idling brain, Cortex
Sleep has been proposed to facilitate inference, insight, and innovative problem-solving. However, it remains unclear how and when the subconscious brain can create novel ideas. Here, we show that cortical offline, but not online, activity is essential for inference evolution and that activity during rapid-eye movement (REM) sleep is sufficient to inspire inference from inadequate knowledge. In a transitive inference paradigm, mice gained the inference one day, but not shortly, after complete training. Inhibiting the neuronal computations in the anterior cingulate cortex (ACC) during post-learning sleep, but not during wakefulness, disrupted the inference without affecting the original memories. Furthermore, after insufficient learning, artificial activation of medial entorhinal cortex-ACC dialogue during only REM sleep created inferential knowledge. These findings establish causal evidence for the necessity and sufficiency of REM sleep in reorganizing existing knowledge to achieve novel inference, thereby highlighting the power of the idling brain in creativity and cognitive flexibility. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-160
Forgetting unveils a temporal transition of engram function.
*Ali Choucry(1,2,3), Kareem Abdou(1,2,3), Reiko Okubo-Suzuki(1,2,3), Emi Murayama(1,2,3), Kaoru Inokuchi(1,2,3)
1. Department of Biochemistry, Graduate School of Medicine and Biological Sciences, University of Toyama, 2. Core Research for Evolutional Science and Technology (CREST), University of Toyama, Toyama, Japan, 3. Japan Science and Technology Agency (JST),University of Toyama, Toyama, Japan
Keyword: Hippocampus, Engram, Forgetting, Behavioral Tagging
Previous memories affect how we approach future events, even those we can no longer consciously recall. It remains unclear how forgotten memories affect new learning in our everyday lives. To address this question, we used an object location memory task in mice and tracked memory degradation across days. The hippocampal engram transitioned from a vocal, readily retrievable state into a mute state that failed to provide spontaneous recall. Interestingly, only the mute state managed to consolidate a weaker, modified memory of the same event, while the vocal state did not. Bidirectional manipulation of the hippocampal engram confirmed the specificity of said consolidation to the mute, but not the vocal state. Both the transition from vocal to mute state and the subsequent consolidation of the weaker event`s memory required the internalization of surface glutamate receptors. We suggest a temporal transition of engram function, with mute hippocampal engrams that no longer support spontaneous recall still affecting the processing of future events. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-161
Orbitofrontal Cortex Governs Wise Decisions Throughout Awake and Sleep States
*Mostafa Reda Fayed(1,2,3), Khaled Ghandour(1,2,3), Reiko Okubo-Suzuki(1,2,3), Kareem Abdou(1,2,3), Emi Murayama(1,2,3), Masanori Nomoto(1,2,3), Kaoru Inokuchi(1,2,3)
1. Grad Sch Med, Univ Toyama, Toyama, Japan, 2. Research Center for Idling Brain Science, Univ Toyama, Toyama, Japan, 3. CREST, JST, Japan
Keyword: Wise Decision Making, Idling Brain, Sleep, Learning and Memory
Wise decisions are supposed to be guided by the accumulated experiences and life skills that are acquired throughout life. It stands to reason that this complex cognitive function requires proper sleep, however, direct experimental evidence is still deficient. For this research project, we intend to investigate the neural underpinnings of wise decision-making, and in what way could this process be affected by sleep. We have established a behavior paradigm that conveyed the knowledge to mice to be able to make a free choice between a mentally challenging choice with a hidden rule to acquire high gain food reward or a simple safe low one. The aforementioned knowledge was conveyed through forced-entrance training sessions on discrete days, where the mice are trained to acquire high gain reward on certain entrances on one side and low guaranteed reward on the other. Normally slept mice can retain their choices on two separate testing days. On the contrary, pre-test sleep deprivation biased the preference away from wise decisions compared to the other testing day. The orbitofrontal cortex (OFC) has been shown to affect value-guided decision-making. We found that chemogenetic silencing of the OFC biased the choices away from rationality. However, this silencing did not further synergize with the deteriorating effect of sleep deprivation. On the contrary, pharmacological over-activation of the OFC triggered the preference towards the wise box to get more pellets. These findings indicate that sleep is essential for wise decisions, where illogical decision pattern of sleep deprivation might be attributed to OFC inactivation. Nevertheless, OFC over-activation boosted the computing abilities and compensated for the effects of sleep deprivation, where it rectified decisions towards rationality. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-162
Brain derived neurotrophic factor rescues amyloid-β induced memory loss via TrkB pathway
*Parul Bali(1), Manjari Rain(2), Bimla Nehru(3), Akshay Anand(2)
1. Department of Biological Sciences, Indian Institute of Science Education & Research-Mohali, India, 2. Neuroscience Research Lab, Dept. of Neurology, PGIMER, Chandigarh, India, 3. Dept. of Biophysics, Panjab University, Chandigarh, India
Keyword: Amyloid-B, Memory loss, Hippocampus, Neurobehavior
Background: Alzheimer’s disease (AD) is one of the untreatable neurodegenerative disorders with associated societal burden. Current therapies only provide symptomatic relief without altering the rate of disease progression. The increased number of failed clinical trials in last two decades indicates the imperative need to explore alternative therapies for AD. Purpose: In this study, we aimed to decipher the role of neurotrophic factors in the reversal of memory loss by recombinant brain derived neurotrophic factor (R-BDNF) in a male mouse model of cognitive impairment induced by intrahippocampal injection of amyloid β-42 (Aβ-42). Methods: The efficacy of R-BDNF therapywas analyzed by neurobehavioral parameters i.e. Morris water maze and passive avoidance after bilateral intra-hippocampal transplantation using stereotaxic surgery. Real-time PCR and immunohistochemistry was carried out in brain tissues in order to analyze the expression of neurotrophic factors, apoptotic, astrocytic and other neuronal cell markers in hippocampus. Results: The administration ofR-BDNF led to reversal of memory loss associated with reduction of Aβ-42 deposition from the brains. The molecular analysis revealed increase in neurotrophic factors i.e. glial derived neurotrophic factor (GDNF), ciliary derived neurotrophic factor (CNTF) and Brain-derived neurotrophic factor (BDNF) after transplantation. The administration of ANA-12, a TrkB inhibitor, reversed the behavioral and molecular effects of R-BDNF suggesting involvement of BDNF-TrkB pathway in the rescue of memory loss. The mRNA expression of caspase 3 was decreased after R-BDNF injection in amyloid-β injured mice, which increased after TrkB inhibition. Bcl2 expression was increased in R-BDNF group. GFAP was increased in R-BDNF injected mice as compared to the TrkB inhibitor group. The expression of Ki67 was significantly higher R-BDNF injected mice as compared to the amyloid injured mice. Conclusion: Our results reveal that R-BDNF therapy can rescue the memory loss by clearance of Aβ mediated by activation of astrocytes. It exerts paracrine effects by modulating the hippocampus neurochemistry as noted by escalation of neurotrophic factors. The increase in neurotrophic factors by R-BDNF may also exert anti-apoptotic effects and may activate complex molecular pathways involving TrkB, RET and Jak-STAT. It will be of interest to dissect the putative molecular pathway in future studies for further insights. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-163
線虫の低温耐性を正に制御する 転写伸長因子TCEB-3の分子遺伝学的解析
Molecular genetic analyses of cold tolerance of C. elegans that is positively regulates by a transcription elongation factor TCEB-3 in the nervous system
*寺西 宏顕(1)、井関 敏啓(1)、高垣 菜式(1)、水口 洋平(2)、豊田 篤(2)、太田 茜(1)、久原 篤(1,3)
1. 甲南大学、2. 国立遺伝学研究所、3. PRIME, AMED
*Hiroaki Teranishi(1), Toshihiro Iseki(1), Natsune Takagaki(1), Yohei Minakuchi(2), Atsushi Toyoda(2), Akane Ohta(1), Atsushi Kuhara(1,3)
1. Konan University, 2. National Institute of Genetics, 3. PRIME, AMED
Keyword: C. elegans , cold tolerance, TCEB-3, ASG thermosensory neuron
Organisms have the ability to adapt to various environmental changes that can be stressful and affect their survival. One of the environmental adaptation abilities is the cold tolerance of C. elegans that is regulated depending on a cultivation-temperature, in which the nervous system, intestine, sperm and muscle coordinately function (Ohta et al., Nat Commun, 2014; Okahata et al., Science Adv, 2019). TCEB-3 is the elonginA known as a conserved transcription elongation factor in a stress-responsive manner (Schneider et. ak, 2004 Mol Brain Res), and tceb-3 mutant showed less cold tolerance. Wild-type worms cultivated at 15℃ can survive at 2℃, however tceb-3 mutant cultivated at 15℃ cannot survive. The decreased cold tolerance in tceb-3 mutants was restored by expression of wild-type TCEB-3 in almost all or about 130 neurons, but not by expression of TCEB-3 in muscle cells or the intestine. These results suggest that multiple neural function of TCEB-3 confers cold tolerance. We have reported that DEG/ENaC DEG-1 is thermo receptor in ASG thermosensory neuron, and that xanthine dehydrogenase XDH-1 functions in AIN and AVH interneurons. Both DEG-1 and XDH-1 are positive regulator for cold tolerance (Takagaki et al., EMBO rep,2020). Our cold tolerance analyses of tceb-3; deg-1 and tceb-3; xdh-1 double mutants suggested that TCEB-3 functions downstream of DEG/ENaC DEG-1 and xanthine dehydrogenase XDH-1. To investigate downstream factors of the transcription elongation factor TCEB-3, we conducted transcriptome (RNA-seq) analysis under 15℃ rearing conditions. As a result, 325 downregulated-genes and 452 upregulated-genes were identified in tceb-3 animals compared to the wildtype strain. The gene ontology categories significantly enriched in the downregulated transcripts including stress response, extracellular material, proteolysis and sperm-related proteins. Interestingly, transcription levels of one GPCR gene that is expressed in thermosensory neuron was downregulated in tceb-3 mutant, and the transcription level of two genes that is known to be involved in cold tolerance were upregulated in tceb-3. We speculated based on these results that a transcription elongation factor TCEB-3 promotes cold tolerance via transcriptional modification. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-164
神経細胞のミトコンドリアのHADHが温度馴化を制御する
HADH in mitochondria of neuron regulates temperature acclimation in C. elegans
*福本 晃久(1)、岡畑 美咲(2)、水口 洋平(3)、豊田 敦(3)、太田 茜(2)、久原 篤(2,4)
1. 甲南大学大学院自然科学研究科、2. 甲南大学 統合ニューロバイオロジー研究所、3. 国立遺伝学研究所、4. PRIME, AMED
*Akihisa Fukumoto(1), Misaki Okahata(2), Yohei Minakuchi(3), Atsushi Toyoda(3), Akane Ohta(2), Atsushi Kuhara(2,4)
1. Grad Sch Nat Sci, Univ of Konan, kobe, Japan, 2. Faculty of Science and Engineering Konan University & Institute for Integrative Neurobiology, Kobe, Japan, 3. National Institute of Genetics, Japan, 4. PRIME, AMED
Keyword: C.elegans, mitochondria
Temperature sensation is essential mechanism for animal to survive and reproduce under continual environmental temperature changes. We are studying cold tolerance and temperature acclimation of C. elegans to analyze the temperature response systems. Cold tolerance is the phenomenon that wild-type animals can not survive at 2 degree after cultivation at 25 degree, whereas 15 degree-cultivated wild-type can survive at 2 degree. Interestingly, When 15 degree-cultivated wild-type is transferred to 25 degrees and stayed for 3 hours, they can not survive at 2 degrees. (Ohta et al., Nature commun, 2014; Okahata et al., Scienceadvances, 2019; Takagaki et al, EMBO rep, 2020). To identify novel genes involved in temperature acclimation, we quantified gene expression-changes under temperature change by RNA sequencing with NGS. Among the genes showing significant expression changes, we focused on hadh gene whose mutant exhibit abnormal increment of temperature acclimation. 3-hydroxy acyl-CoA dehydrogenase (HADH) which is known to catalyze mitochondrial fatty acid β-oxidation in human. GFP reporter analysis suggested that HADH is expressed in intestine and several neurons. The abnormal temperature acclimation of hadh mutant was rescued by expressing hadh cDNA in 13 pairs of neurons including mechano-sensory neurons, but was not rescued in intestine. To identify the organelle where HADH regulates temperature acclimation, we conducted subcellular localization analysis, and HADH protein was localized in the mitochondria of neuron. These suggested that HADH in mitochondria of neuron could regulate temperature acclimation. We are now trying to identify the functional neuron where HADH regulates temperature acclimation. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-165
Role of Eph-ephrin signal on anatomical and functional module in the medial entorhinal cortex
*Naoki Yamamoto(1), Hisayuki Osanai(1), William D Marks(1), Mark Henkemeyer(2), Takashi Kitamura(1)
1. Dept of Psychiatry, Univ of Texas Southwestern Medical Center, Dallas, Texas, USA, 2. Dept of Neuroscience, Univ of Texas Southwestern Medical Center, Dallas, Texas, USA
Keyword: Entorhinal cortex, Eph-ephrin, Functional module, Spatial Memory
The layer II of medial entorhinal cortex (MECII) has characteristic hexagonally arranged cell clusters of Wolfram syndrome1 (Wfs1)+ pyramidal cells surrounded by Reelin+ stellate cells. Accumulating evidence from neurophysiological and neuroimaging studies suggests that cells coding similar spatial information tend to be clustered in MECII, implicating that the Wfs1+ cell clusters may generate the functional modules which contributed to the processing of spatial information and memory. However, it remains unknown the molecular basis for the formation of anatomical cell clusters in MECII and how the anatomical modules affect functional modules. Here, we hypothesized that the cell clusters may be generated by cell-cell-mediated interaction/repulsion. We first comprehensively examined expression patterns of EphBs/ephrin-Bs genes, which are well known as initiators of cell-contact-mediated repulsion signals by fluorescent in situ hybridization (FISH). Among EphB/ ephrin-B family genes, EphB1 and ephrin-B2 were selectively expressed in MECII on adult stage. Double-FISH analysis revealed that EphB1 was expressed in Reelin+ cells, while ephrin-B2 was expressed in Wfs1+ cells. Furthermore, we revealed ephrin-B2+ cells in the layer V of MEC postnatally migrated to Reelin and EphB1+ layer II and formed cell cluster during developmental period. Loss-of-function studies using EphB/ephrin-B genes knockout (KO) revealed that the cell clusters were scattering in the ephrin-B2 hetero knockout (EB2) mice. On the other hand, the cell clusters were maintained after adult-onset ephrin-B2 conditional KO. These results suggest that the EphB1/ephrin-B2 signaling between Reelin+ and Wfs1+ cells are critical for formation of cell clusters in the MECII during early postnatal stage. Next, to examine whether anatomical arrangement of cells coding similar spatial information in MECII was impaired in the EB2 mutant, we conducted in vivo Ca2+ imaging of MECII in free-moving mouse during open field exploration. Clear the hexagonally arranged periodic firing fields of grid cells was observed on Reelin+ stellate cells in WT animals. Grid cells with similar phase were in small anatomical range and formed the grid phase cluster in WT. On the other hand, grid activity was impaired in EB2 mutant, and the grid phase cluster was significantly obscured. These results supported the hypothesis that the anatomical structure in MECII may provide geometrical platform for regulation of grid activities. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-166
線虫C. elegansのスプライシング因子AQRが関与する高温および低温耐性
High and low temperature tolerance regulated by the splicing factor AQR in C. elegans
*佐藤 夕希(1,2)、礒野 一帆(4)、太治 輝昭(4)、太田 茜(1,2)、久原 篤(1,2,3)
1. 甲南大学大学院自然科学研究科、2. 甲南大学統合ニューロバイオロジー研究所、3. PRIME, AMED、4. 東京農業大学 バイオサイエンス学科
*Yuki Sato(1,2), Kazuho Isono(4), Teruaki Taji(4), Akane Ohta(1,2), Atsushi Kuhara(1,2,3)
1. Grad Sch of Natural Science, Konan Univ, Kobe, Japan, 2. Institute for Integrative Neurobiology, Konan Univ, Kobe, Japan, 3. PRIME, AMED, 4. Tokyo University of agriculture, Tokyo, Japan
Keyword: emb-4
Adaptation to changes in environmental temperature caused by seasonal and diurnal changes is an important ability for organisms to survive and reproduce. The nematode C. elegans modifies its cold tolerance to 2°C, depending on the previous cultivation temperature. Previous and recent our studies revealed that cold tolerance is cooperatively regulated by multiple thermoreceptor neurons, gut, sperm, and muscle. Here we report that emb-4 gene, which encodes a spliceosomal protein, was found to be involved in both cold tolerance and high temperature tolerance, which enable survival even when exposed to temperatures as low or high as 2°C or 31°C, respectively. Temperature tolerance is essential for not only animals but also plants. Analysis of polymorphic Arabidopsis plants has shown that polymorphisms in the splicing factor AQR (Aquarius intron-binding spliceosomal factor) make natural variation in high temperature tolerance (Isono et al., unpublished). The mutation in emb-4 gene that is a C. elegans homolog of AQR caused abnormal decrease of high temperature tolerance than that of the wild-type N2 strain. By contrast, the emb-4 mutant showed the enhanced-cold tolerance than the wild strain. These suggests that a common molecule among plants and animals is involved in temperature tolerance, and EMB-4 positively regulates cold tolerance and negatively regulates high-temperature tolerance. In order to identify genes that function downstream of the spliceosomal protein EMB-4, we performed transcriptome analysis under various temperature stimuli, by using NGS. In comparison between emb-4 mutant and wild-type that were cultivated at 20°C and transferred to 2°C for 9 hours, the expression levels of about 800 genes were significantly increased. Also, in comparison between emb-4 and wild-type cultivated at 20°C and transferred to 32°C for 1 hour, the expression levels of about 133 genes were significantly increased. Regardless of temperature conditions, the expressions of genes involved in stress response, innate immunity, and cuticle organization were significantly altered in emb-4 mutant. Among these genes, the mutation in acid sphingomyelinase (asm), phospholipid scramblase (scrm), and novel gene C38D9.2 expressed in intestinal cells, caused abnormalities in high and cold temperature tolerance. We are currently analyzing these mutants to elucidate the temperature adaptation mechanism involving EMB-4. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-167
キイロショウジョウバエにおける歌の嗜好性に経験依存的な変化をもたらす神経修飾メカニズムの解明
Elucidating the Neural Modulatory Mechanism of Experience-dependent Changes of Song Preferences in Drosophila melanogaster
*千葉 悠希奈(1)、大橋 拓朗(1)、Li Xiaodong(1,2)、上川内 あづさ(1)
1. 名古屋大学理学研究科、2. カリフォルニア大学サンタバーバラ校
*Yukina Chiba(1), Takuro Ohashi(1), Xiaodong Li(1,2), Azusa Kamikouchi(1)
1. Grad Sch Sci, Nagoya University, Aichi, Japan, 2. University of California, Santa Barbara, California, U.S.A
Keyword: Drosophila melanogaster, learning, neuromodulation, experience-dependent behaviors
How do animals’ past auditory experiences affect their behaviors today? We know that postnatal auditory experiences are important in language acquisition in humans and in the learning of species-specific courtship songs in zebra finches. However, current knowledge has a large gap between our understanding of experience-dependent behavioral changes and its systems-level mechanisms. To bridge this gap of knowledge, we use a simple model system, the fruit fly Drosophila melanogaster. Fruit flies have species-specific courtship songs, which are produced by wing vibrations in males during courtship. Previous studies showed that female flies that are subjected to conspecific courtship songs reduce receptivity towards heterospecific songs, suggesting experience-dependent learning. By leveraging fruit fly’s powerful genetic tools, we aimed to determine the neural basis of song preference learning. Current studies suggest that neurons that express Gad1, a gene encoding for an enzyme for GABA synthesis, mediate song preference learning. To identify how the Gad1 expressing neurons encode song preference learning, we hypothesized that song experience changes GABAergic neurons functionally by changing their responses to upstream neurons. Considering that monoaminergic signals control the strength or switch of behavior, we examined their roles in song learning by knocking down their receptors in GABAergic neurons. Through behavioral analyses, we found that the knockdown of a single type of serotonin receptor was sufficient to disrupt song learning ability. Interestingly, a knockdown of the other types of serotonin receptors or GABA receptors did not cause learning impairment. Motivated by this finding, we immunohistochemically identified a total neuronal population of about 40 neurons that is GABAergic and expresses the responsible serotonin receptor. About eight of them are located around the antennal lobe, 10 in the superior neuropils including in the region of pars intercerebralis, and 14 in the anterior ventrolateral neuropils in the fly brain. Together, this finding underscores the significance a single receptor in a circuit can have for executing fine-tuned behaviors. Importantly, serotonin is known to modulate GABAergic neurons in human language acquisition. Therefore, the finding gives further insight into the conservation of auditory learning mechanisms in both vertebrates and invertebrates. We plan to further understand the function of the serotonin receptor by examining their specific roles in the song learning process. Through the examination of the auditory system in the fruit fly, we hope to paint a comprehensive picture of how experiences are encoded in the brain, which allows animals to better adapt to the ever-changing environment. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-168
Identification of pathway-specific local field potentials in the entorhinal cortical-hippocampal networks
*Hisayuki Osanai(1), Jun Yamamoto(1), Sachie Ogawa(1), Kaoru Inokuchi(3,4,5), Takashi Kitamura(1,2)
1. Dept of Psychiatry, Univ of Texas Southwestern Medical Center, Dallas, Texas, USA, 2. Dept of Neuroscience, Univ of Texas Southwestern Medical Center, Dallas, Texas, USA, 3. Dept of Biochemistry, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Sugitani, Toyama, Japan. , 4. CREST, JST, University of Toyama, Toyama, Japan. , 5. Research Center for Idling Brain Science, University of Toyama, Toyama, Japan
Keyword: Independent component analysis, Local field potential, Multichannel electrophysiology, Hippocampus
How brain areas communicate is important question but still unresolved. Input of neural oscillatory activities from other brain areas have been proposed to play a crucial role in this process through modulation of spiking activities. Traditionally, lesion experiments have been conducted to investigate the influence of other areas. However, lesion experiments cannot elucidate the original dynamics of neural pathways before lesion. Recently, independent component analysis (ICA) has started to be used as a mathematical tool to disentangle local field potential (LFP) signals to specific input-pathway’s activities. The conventional technique separates independent components (ICs) from original LFP by ICA, and speculates that the separated ICs are of the specific input-pathway using the anatomical location information of ICs. However, this method has limitations: First, it is not guaranteed that the selected component is truly of the speculated pathway. When multiple inputs are on the overlapping layers, e.g., the input pathways of medial entorhinal cortex layer II pyramidal cells (MECIIp) to CA1 lacunosum layer and layer III cells (MECIII) to CA1 lacunosum-moleculare layer, it is difficult to distinguish these pathways. Second, the selection of IC can be biased by the researcher, because only one IC is selected in the conventional methods although it is possible that a single cell-type pathway can generate multiple ICs. In order to overcome these limitations, we propose a novel method to investigate input activities by ‘tagging’ the pathway-associated components with optogenetics stimulation, instead of using the anatomical locations information in the conventional method. In the current study, a 32-ch silicon probe and an optical fiber were implanted into hippocampal CA1 of the mice expressing ChR2 in MECIIp or MECIII in order to record spontaneous and opto-response LFP. After ICs are separated from the LFP by ICA, the ICs are categorized as “tagged” if the IC’s opto-response exceed z-score threshold. Then, pathway associated LFPs are reconstruct from all “tagged” ICs. On average, six ICs are categorized as “tagged” both in MECIIp and in MECIII pathway-stimulated mice, while tagged ICs were absent in ICs obtained from wild-type mouse LFPs. In both cases of MECIIp and MECIII, the reconstructed LFP showed the absence of sharp wave ripple events while they can be observed in original LFPs. We further investigated the differences of MECIIp and MECIII pathways in oscillatory power, theta-phase differences, and theta-gamma couplings, comparing early and late phase of an animal's exposure to a novel environment (linear track). Our results show that this opto-ICA technique can successfully dissect field potential signals generated by specific cell-type input pathways. Compared with the conventional method, our method has advantages of cell-type specific and less-biased analysis. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-169
匂い記憶保持に必要な条件付後のドーパミン放出を制御する神経機構
Neuronal mechanisms underlying post-associative dopamine release for olfactory memory consolidation
*長野 慎太郎(1)、齊藤 実(1)
1. （公財）東京都医学総合研究所
*Shintaro Naganos(1), Minoru Saitoe(1)
1. Tokyo Metropolitan Institute of Medica Science
Keyword: Dopamine, Olfactory memory, Drosophila
Dopamine (DA) is a monoamine neurotransmitter and regulates various higher brain functions including learning and memory. In Pavlovian classical conditioning, it is thought that DA release is induced by unconditional stimulus (US) and reinforces the relationship between the conditional stimulus (CS), and the conditional response. In this study, we have found that DA is induced in consequence of a CS-US association, which regulates olfactory aversive learning in Drosophila. PPL1-γ1pedc dopaminergic neurons (DANs) projecting to the g1 compartment of the mushroom body (MB) lobe release DA by not only US but CS presentation and during olfactory conditioning (CS-US association). However, suppressing neuronal output of PPL1-γ1pedc DANs did not affect olfactory learning. By contrast, inhibiting neuronal output of PPL1-γ1pedc DANs immediately after olfactory conditioning attenuated olfactory learning, suggesting that DA release after olfactory conditioning but not during conditioning is involved in olfactory aversive learning. We employed in vivo DA imaging to study DA release from PPL1-γ1pedc DANs in olfactory aversive conditioning and found that tonic DA release occurs after olfactory conditioning (post-associative DA release: PADR). We conducted pharmacological screening to investigate neuronal molecules underlying PADR and found a number of candidate molecules. One of those, the glycogen synthase kinase 3 (GSK3) functioned in mushroom body output neurons (MBON) but not in DANs and regulated olfactory aversive memory. Importantly, suppressing GSK3 activities in γ1pedc MBONs inhibited PADR from PPL1 γ1pedc DANs and olfactory aversive learning, suggesting that GSK3 activities in γ1pedc MBONs regulate olfactory aversive memory via PADR from PPL1-γ1pedc DANs. Our findings also suggest that PADR contributes to consolidation but not acquisition of olfactory memory by CS-US association in the MBs. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-170
Neural bases for song preference to familiar songs in female zebra finches
*Yung Chieh Liu(1), Yoko Yazaki-Sugiyama(1,2)
1. Okinawa Institute of Science and Technology, Okinawa, Japan, 2. International Research Center for Neurointelligence, The University of Tokyo, Tokyo, Japan
Keyword: Song preference, Auditory cortex, Song memories, Female zebra finch
Zebra finch males learn to sing by memorizing and mimicking their father’s songs during development for attracting females. On the other hand, females show spatial approaches or reinforced behaviors to familiar (normally their father’s) songs (Clayton, 1988; Riebel, 2000), suggesting that they also form song memories in their brain by hearing adult male songs during development. Neurons in the secondary auditory cortex, caudomedial nidopallium (NCM) and caudomedial mesopallium (CMM) show auditory responsiveness to familiar songs (Terpstra et al., 2006), however, the neural bases for song memory formation and/or song recognition in females has remained unclear. Here we explored if the NCM and/or CMM in female zebra finches involves the neuronal substrates for father song memory as a basis for song preference behavior. We employed a two-operant choices preference test, perch-hop assay, and found that females showed a significantly weaker preference to their fathers’ songs after bilateral chemical lesions of the CMM. Females with bilateral sham lesions (PBS injection) did not change their preference. Furthermore, we induced apoptosis in the CMM neurons which responded to the playback of their father’s songs by using adeno-associated viral vectors (AAV-cFOS-Tet-ON-Caspase3 and AAV-cFOS-Tet-ON-DTA). These females also showed a decreased preference to their fathers’ songs after the inductions of neuronal cell death. Taken together, our results suggest that CMM holds neurons for father song memories and that are involved for song preference behavior. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-171
Motopsin過剰発現マウスは新規環境下で過活動を示し，成体期でのmotopsin過剰発現の抑制は行動障害を改善しない
Mice overexpressing motopsin show hyperactivity in a novel environment, that is not restored by the suppression of transgenic motopsin in adulthood.
*宮田 栞(1)、津田 雅之(2)、三井 真一(1)
1. 群馬大学大学院保健学研究科リハビリテーション学講座、2. 高知大学総合研究センター動物資源開発分野
*Shiori Miyata(1), Masayuki Tsuda(2), Shinichi Mitsui(1)
1. Dept. of Rehab. Sci., Grad. Sch. of Health Sci., Gunma Univ., Gunma, Japan, 2. Div. of Lab. Animal Sci., Sci. Res. Cen., Kochi Univ., Kochi, Japan
Keyword: motopsin, Na-K-ATPase, hyperactivity, spatial memory
Motopsin is a secreted serine protease that is highly expressed in various brain regions during the early postnatal period and plays a crucial role in synaptogenesis via Na-K-ATPase (NKAα3) activity. Motopsin deficiency causes severe intellectual disability in humans, and impairs spatial memory with involving decreased spine density in mice. Administration of the agrin fragment, an extracellular substrate of motopsin, restores filopodia formation in motopsin-deficient hippocampal slice. However, it is unclear whether motopsin overexpression affects behaviors via enhanced synaptogenesis. Here, we designed the transgenic (DTG) mice doxycycline (Dox)-dependently overexpressing motopsin in the brain with the Tet-Off system.
We investigated the spontaneous activity in adult DTG mice, compared with control littermates and DTG mice that the transgenic motopsin expression was suppressed by Dox administration for 3 weeks. To evaluate spatial memory, cognitive function and anxiety behavior, DTG mice were assessed on the Barnes maze test (BM), an open field test (OF), followed by a novel object recognition test (NOR). Brains were prepared for NKAα3 activity measurement and for the immunohistochemical analyses of motopsin and cFos 90 min after the NOR.
DTG mice showed hyperactivity in the first dark period after transferring to the measurement device, compared with the control group. In the BM, DTG mice delayed the latency to reach the goal. Interestingly, DTG mice reduced moving distance in the maze regardless of Dox administration. In the OF, DTG mice did not show anxiety behavior, but Dox administration increased the center stay ratio. In the NOR, DTG mice increased the total object sniffing time, but the ratio of novel object sniffing time against total sniffing time did not change. The NKAα3 activity in the cortex and hippocampus was comparable between genotypes or Dox administration. The overexpression level of motopsin varied among individuals, but showed no correlation with the observed behavioral measurements.
Our results suggest that motopsin overexpression from the developmental period induces hyperactivity in a novel environment and impairs spatial memory without affecting NKAα3 activity. The normalization of motopsin expression in adulthood does not restore the behavioral deficits. Therefore, motopsin may be important for the establishment of neuronal circuits for spontaneous activity and spatial memory during the developmental period. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-172
時間に基づいた報酬予測を制御する脳内ドーパミン放出の解析
Analysis of dopamine release during temporal reward expectation in mice
*松本 悠真(1)、小澤 貴明(1)、柴田 智弘(1)、中村 萌(1)、岩本 涼太郎(1)、尾山 賀信(1)、Macpherson Tom(1)、疋田 貴俊(1)
1. 大阪大学 蛋白質研究所
*Yuma Matsumoto(1), Takaaki Ozawa(1), Tomohiro Shibata(1), Moe Nakamura(1), Ryotaro Iwamoto(1), Hironobu Oyama(1), Tom Macpherson(1), Takatoshi Hikida(1)
1. Institute for Protein Research, Osaka University, Osaka, Japan
Keyword: dopamine, interval timing, imaging, striatum
Time passes ubiquitously for all living organisms on the earth. However, subjective perception of time can be altered depending on various external environmental conditions and changes in the internal state of the mind. Different biological mechanisms of time perception are known to account for events occurring at different time scales, which may range from seconds to sometimes years. Interval timing, used when perceiving events occurring at second to minute time scales, is particularly important for adaptive decision making. It has been suggested that midbrain dopamine neurons, characterized well for their functions in reward-related behavior, also play an important role in regulating the perception of interval timing. Pharmacological studies have proposed the dopamine clock hypothesis, which suggest that elevated dopamine release in the brain accelerates the subjective passage of time (i.e., making feel the time length longer). On the other hand, another recent study using pathway specific optogenetic manipulation has suggested that the activation of the nigrostriatal dopamine pathway deaccelerates the subjective passage of time in mice.
Given these contradicting views, it is necessary to re-examine the role of dopaminergic pathways in the perception of interval timing. Use of the fluorescent dopamine sensor protein GRAB-DA has made dopaminergic recording at high temporal resolutions possible, and allows for more detailed examination of dopaminergic signaling during behavioral tasks. In this study, we recorded the changes in dopamine signaling during a cue-guided temporal reward expectation task. In this task, head-fixed mice were presented with a liquid reward (sweetened milk) if they could successfully lick a spout after a set duration of time (3 or 6 seconds) during auditory cue presentation (3 or 9 kHz). We found that mice showed a ramping-up of anticipatory lickings during each cue, and their peak time points were temporally separated depending on the set duration (i.e., 3 or 6 seconds). This suggests that mice can discriminate the time of reward delivery based on a preceding auditory cue. Furthermore, we discovered associations between stratal dopamine release and timed behavior, suggesting potential roles of striatal dopamine release in the perception of interval timing. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-173
Visual self-image in the mouse hippocampus
*JUN YOKOSE(1), WILLIAM D MARKS(1), SACHIE K Ogawa(1), JUN YAMAMOTO(1), TAKASHI KITAMURA(1,2)
1. Dept Psy, Univ of Texas Southwestern Medical Center, Dallas, USA, 2. Dept Neurosci, Univ of Texas Southwestern Medical Center, Dallas, USA
Keyword: HIPPOCAMPUS, VISUAL RECOGNITION, LEARNING AND MEMORY, SOCIAL EXPERIENCE
The experience of self as the object of attention, which is psychologically known as self-awareness, facilitates animals to reflect on their actions and understand the extent to which those actions match personal values as well as group standards in society. The ability to utilize self-relevant information is autobiographically formed through the life with others, which is critical for survival. However, how neural circuits enable behavioral adaptation to recognize and form the self-image remains unknown. Here, we established a mirror-induced visual recognition of self-image (MVRS) task in mice. After mirror familiarization in C57BL/6J mice, the mice with white ink stained on their head more frequently and specifically groomed depending on the amount of the ink compared to the mice with black ink. We refer this as mark-directed behavior. Mice did not show mark-directed behavior without the mirror familiarization. Since the ink attachment itself sightly but significantly increased a head-grooming behavior under dark condition, we speculate that a mark-directed behavior requires not only visual perception stimulus by mirror reflection but also some tactile perception on their head in mice MVRS. Interestingly, post-weaning socially isolated mice failed to show the mark-directed behavior. Chemogenetic inhibition of neural activity of hM4(Gi)-expressing neurons in dorsal hippocampal CA2 region (dCA2) or ventral hippocampus (vHPC) during the MVRS test demonstrated the requirement of vHPC activity but not dCA2. We further investigated neural activity of vHPC neurons, especially CA1 region, during the MVRS test by the activity-dependent cell tagging. The subpopulation of vCA1 neurons activated during homecage with mirror were significantly reactivated during the second mirror exposure and interaction with both familiar and stranger C57BL/6J mice, but not stranger FVB/NJ mice. Inactivation of the subpopulation of vCA1 neurons activated by the mirror exposure in homecage attenuated the mark-directed behavior. Our study suggests that the subpopulation of vCA1 stores a visual self-image, which is developed through the social interaction with others. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-174
聴覚性刺激を手がかりとした学習行動における視床線条体入力
Thalamostriatal input in learning behavior cued by auditory stimuli
*加藤 成樹(1)、小林 和人(1)
1. 福島県立医科大学
*Shigeki Kato(1), Kazuto Kobayashi(1)
1. Fukushima Medical University
Keyword: Thalamus, Striatum, Learning, Retrograde vector
The thalamus is composed of many nuclei, with different cell types forming a mosaic structure. The input-output relationship between various subregions of the cerebral cortex and the thalamus has been reported to play an important role as a hub for receiving stimuli from the outside world and processing and transmitting the information in the brain. On the other hand, there are few informations on the input system from the thalamus to the striatum. Anatomical reports and recent connectome analyses have revealed that there is a very strong glutamatergic projection from the parafascicular nucleus (PF) and the central lateral nucleus (CL) of the intralaminar thalamic nucleus to the striatum, which contacts the medium-sized spiny neurons of the striatum via cholinergic neurons. To clarify the behavioral physiological significance of this input, we used retrograde viral vectors (HiRet; Kato et al., 2011a, b and NeuRet; Kato et al., 2011c, 2014, 2019, 2020) in a learning behavioral test with operant conditioning cued by visual stimuli, and molecular genetic techniques were combined to analyze the behavioral function of model mice in which the thalamostriatal pathway was selectively removed. As a result, we found that learning acquisition and executive functions were significantly impaired in that thalamostriatal pathway removal group (Kato et al., 2011b, 2018). In addition, recent analyses have shown that the activity of the striatum varies greatly in a region-specific manner depending on the timing of the learning processes. In order to get closer to the physiological neural function of the thalamostriatal input in animals during a behavioral task, we examined whether changing the experimental condition to rats, the reward to liquid, and the visual input to auditory stimulation would produce results similar to the previously obtained contribution to the learning function in the thalamostriatal pathway. The visual stimulus was the presence or absence of the illumination lamp, while the auditory stimulus was the discrimination between 2 kHz and 10 kHz. Also, instead of rewarding food, we gave water. Next, open field tests were conducted to determine if there were any effects on basic motor functions. The latest data will be presented along with the results of these analyses.
Kato et al., 2011a: Hum. Gene Ther., 22, 197-206, (2011).
Kato et al., 2011b: J. Neurosci., 31, 17169-17179, (2011).
Kato et al., 2011c: Hum. Gene Ther., 22, 1511-1523, (2011).
Kato et al., 2014: J. Neurosci. Methods, 227, 151-158, (2014).
Kato et al., 2018: Cell Rep., 22, 2370-2382, (2018).
Kato et al., 2019: J. Neurosci. Methods, 311, 147-155, (2019).
Kato et al., 2020: J. Neurosci. Methods, 311, 108854, (2020). | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-175
The relationships between cognitive function and eating behavior in young Korean adults
*Young-A Lee(1), Jae-Won Jung(1), Na-Hyun Kim(1), Yukiori Goto(2), Kyung-A Lee(1)
1. Dept Food Sci & Nutr, Daegu Catholic Univ, Gyeongsan, South Korea, 2. Primate Res Inst, Kyoto Univ, Aichi, Japan
Keyword: Eating behavior, Reward sensitivity, Working memory, Cognition
Eating behavior could be associated with various psychiatric disorder that cause cognitive dysfunction. Along with eating disorder, for instance, patients with substance use disorder exhibit abnormal eating behavior, which could be due to a compensation mechanism of the reward system. Moreover, accumulating evidence suggest that food consumption itself could be addicted, known as food addiction. However, it is still unclear what cognitive function may be associated with eating behavior, and how cognitive dysfunction results in abnormal eating behavior. As a first step to address this issue, in this study, we investigated relationships between cognitive function and eating behavior in young Korean adults. Fifty healthy adults (25 males and 25 females) aged from 20 to 30 years old were recruited for the study. The adult eating behavior questionnaire, assessing 8 dimensions of eating behavior, such as Enjoyment of Food (EF), Emotional Over-Eating (EOE), Emotional Under-Eating (EUE), Food Fussiness (FF), Food Responsiveness (FR), Hunger (H), Slowness in Eating (SE) and Satiety Responsiveness (SR), was administered. Cognitive functions of participants were evaluated with the psychological tests for visual working memory and reward sensitivity. Multiple regression analysis unveiled that EUE and SR were associated with visual working memory and EF, FF, and SR were associated with reward sensitivity. These results suggest that some aspects of eating behavior are associated with cognitive function; therefore, eating behavior may be used to predict cognitive function. We are currently conducting AI analysis to further investigate the associations, and in future studies, we will investigate how such relationships may be associated with the dopamine and serotonin systems and may be altered in psychiatric disorder. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-176
ラットは不確実性が高い状況下において情報希求行動を増加させる
Rats increase information seeking behavior under uncertainty
*結城 笙子(1)、櫻井 芳雄(2)、柳原 大(1)
1. 東京大学大学院総合文化研究科、2. 同志社大学大学院脳科学研究科
*Shoko Yuki(1), Yoshio Sakurai (2), Dai Yanagihara(1)
1. Graduate School of Arts and Sciences, The University of Tokyo, Tokyo, Japan, 2. Graduate School of Brain Science, Doshisha University, Kyoto, Japan
Keyword: metacognition, information-seeking, interval timing, rats
Metacognition is the ability to adaptively control one's behavior by referring to one's own cognitive processes. This ability allows animals to change their behavior based not only on the external environment but also on their own state, and thus is thought to be beneficial for learning in situations where external information is not sufficient. Metacognition in animals has already been studied in primates, birds, and rodents. In these previous studies, optimal behavior in a task that has been intensively trained beforehand was considered as evidence of metacognition. Therefore, it has been criticized those behaviors which appear to be based on metacognition are simply habitual behaviors formed by conditioning.
To address this criticism, we tested whether rats exhibit non-habitual metacognition in the form of information-seeking behavior: intensive search for information necessary to perform a task in uncertain situations, such as early learning or when exposure to discriminative stimuli is restricted.
The experimental setup was an operant chamber which had a nose-poke hole in the center of each of the two opposing sides. The behavioral task was started by lighting one of the holes, and when the rats continued to respond to the hole for a certain period, the other hole was dimly lit. The rats were then rewarded with water if they responded to the opposite hole within two seconds of the lighting. In other words, the task required the rat to look back at the other side while responding to the first hole and seek information about whether the other hole was lit or not.
We analyzed the behavior of rats during the task using a high-speed camera and found that the looking-back behavior appeared immediately after switching the time until the opposite hole was lit, and gradually decreased. With this decrease, the timing of the looking back became closer to the time the opposite hole was lit. Furthermore, when the task was modified so that rats could know whether the opposite hole was lit or not without looking back, the frequency decreased significantly. These results suggest that the rats controlled their behavior according to the amount of the necessary information they themselves possessed to perform the task. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-177
メトホルミンはBTBRマウスにおける自閉症関連行動と内側前頭前野の興奮性/抑制性バランス異常を改善する
Metformin improves Autism-relevant behaviors and excitatory/inhibitory imbalance in the medial prefrontal cortex in BTBR T+tf/J mice
*池原 実伸(1)、山室 和彦(1)、岡村 和哉(1)、法山 勇樹(1)、遠藤 のぞみ(2)、杉村 岳俊(3)、西 真弓(2)、齋藤 康彦(3)、牧之段 学(1)
1. 奈良県立医科大学精神医学講座、2. 奈良県立医科大学第一解剖学講座、3. 奈良県立医科大学第一生理学講座
*Minobu Ikehara(1), Kazuhiko Yamamuro(1), Kazuya Okamura(1), Yuki Noriyama(1), Nozomi Endo(2), Taketoshi Sugimura(3), Mayumi Nishi(2), Yasuhiko Saito(3), Manabu Makinodan(1)
1. Department of psychiatry, Nara Medical University, 2. Department of Anatomy and Cell Biology, Nara Medical University, 3. Department of Neurophysiology, Nara Medical University
Keyword: autism, rule-shift learning, electrophysiology, metformin
Autism spectrum disorder (ASD) is a cluster of neurodevelopmental disabilities characterized by defective social interactions, impaired communication and restricted and repetitive behaviors. Although the global incidence of ASD has increased over time, the etiology of ASD is poorly understood, and there is no effective pharmacological intervention for treating ASD. Therefore, it is urgent for efficacious treatments to be developed to prevent and treat ASD. Recent studies have suggested that metformin has the potential to treat ASD. A recent study has also shown that metformin corrected social deficits, reversed increased self-grooming and reduced the incidence of seizures in the adult fragile X syndrome mouse model. In addition, one study showed that early metformin treatment may have beneficial effects on ameliorating behavioral deficits in BTBR T+tf/J mice. These data suggest that metformin may have the potential to counteract the cognitive and behavioral deficits shown in ASD models. However, we have unknown whether metformin treatment have effectiveness for rule shift learning based on what neural circuit mechanism in medial prefrontal cortex (mPFC).
In this study, Water T maze showed that persistent behavior is significantly enhanced in BTBR compared to C57BL/6 mice at 60-70 days. To elucidate this neural mechanism, We recorded excitatory and inhibitory synaptic transmission from pyramidal cells in layer Ⅴ/Ⅵ of the mPFC using the whole-cell patch-clamp technique. We found that both spontaneous and miniature excitatory post-synaptic currents frequencies significantly increased in BTBR mice compared to C57BL/6 mice. In contrast, both spontaneous and miniature inhibitory post-synaptic currents frequencies significantly reduced in BTBR mice compared to C57BL/6 mice. These data suggested that BTBR mice have excitatory/inhibitory (E/I) imbalance in synaptic transmission in pyramidal cells of layer Ⅴ/Ⅵ of the mPFC. We next sought to determine whether chronic restoration of Layer V/VI neurons activity is sufficient to ameliorate rule-shift learning in adult BTBR mice. A micro-osmotic pump with either saline or metformin in saline (200 mg/kg for 14 days) was implanted subcutaneously into each mouse under sterile procedures. Metformin treated mice rescued rule-shift learning in the water T maze, with no impact on motor activity or measurements of anxiety-related behavior in BTBR mice.
These results indicate that disrupted E/I balance in synaptic transmission in pyramidal cells of layer Ⅴ/Ⅵ of the mPFC in BTBR may be involved in the enhancement of persistent behavior in BTBR mice, and metformin might have a potential of rescue for autism-relevant behavior. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-178
Fluorescent sensor reveals dopamine dynamics in the primate striatum
*Gaoge YAN(1), Hidetoshi AMITA(1), Satoshi NONOMURA(1), Ken-ichi INOUE(1), Masahiko TAKADA(1)
1. Primate Res Inst, Kyoto Univ, Aichi, Japan
Keyword: Monkey, Basal ganglia, Reward, Imaging
Dopamine neurons encode reward prediction error (RPE), which represents the difference between predicted and actual reward. It is well known that dopamine neurons in primates are more activated by unpredicted reward than predicted reward, and that their activity is suppressed by unpredicted no-reward (Schultz et al., 1997). However, which striatal region receives the RPE signal remains unclear, because it is difficult to detect dopamine signals from extensive regions of the striatum (i.e., the caudate nucleus, putamen, and ventral striatum) by means of conventional approaches.
dLight1, a recently-developed fluorescent dopamine sensor, reveals dopamine dynamics with high specificity and temporal resolution in rodents. It is, therefore, required to apply this technique to the primate brain for elucidating various dopamine functions in the basal ganglia and related cortical areas. Here, we investigated whether dLight1 is useful for detecting dopamine signals in primates.
First, we injected a newly-prepared AAV2.1-CaMKII-dLight1.1 vector into the rat striatum and confirmed a high level of dLight expression therein. Employing fiber photometry, we then recorded dLight signals from the striatum during the performance of a stimulus-reward association task and found that the signals were accentuated by unpredicted reward and conversely dampened by unpredicted no-reward. Next, we applied the same vector system to the monkey striatum. We successfully and repetitively recorded the dLight signals from diverse striatal regions over months. Consistent with the data obtained in the rat, the signals at specific striatal sites were enhanced with unpredicted reward while depressed with unpredicted no-reward.
The present study has demonstrated the validity of dLight1 in primates and identified the striatal regions receiving the RPE signal from dopamine neurons. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-179
Functional brain network reconfiguration changes across repeated movie-viewing and differentially associates with free recall performance
*Wan Lin Yue(1,2), Kwun Kei Ng(1), Xing Qian(1), Amelia Jialing Koh(1), Kian Foong Wong(1), Kai-Yen Chang(3), Shuping Lim(1,4), Angelica Ting Yi Ang(4), Michael W L Chee(1,5), Juan Helen Zhou(1,2,5,6)
1. Centre for Sleep and Cognition, Yong Loo Lin School of Medicine, National University of Singapore, 2. Integrative Sciences and Engineering Programme, NUS Graduate School, National University of Singapore, 3. Department of Psychiatry and Psychotherapy, University Hospital, LMU Munich, Munich, Germany, 4. National University of Singapore, 5. Centre for Translational MR Research, Yong Loo Lin School of Medicine, National University of Singapore, 6. Department of Electrical and Computer Engineering, National University of Singapore
Keyword: naturalistic paradigm, functional reconfiguration, free recall, movie-viewing
Studies of functional connectivity (FC; temporal synchrony of brain activity from different regions) revealed that intrinsic functional networks have preserved overall architecture between rest and task. More efficient functional brain reconfiguration (higher FC similarity) between rest and task was previously found to be associated with better cognition. However, it remains unclear how this functional reconfiguration is relevant for naturalistic conditions. Furthermore, how functional reconfiguration and its association with behaviour may change across sessions has yet to be investigated. Here, we studied network-level functional brain reconfiguration across repeated movie-viewing and how this relates to free recall scores. We analysed fMRI scans over 3 days in a cohort of healthy young adults (N = 28, 12 males, 26.5 ± 2.9 years). In each session, participants underwent a resting state scan, then viewed 3 movie clips (The Circus, Indiana Jones, Inscapes) in a randomised order. The same clips were used in each session. After the 3rd session, free recall was collected for Circus and manually scored by 3 independent raters through a consensus approach. Using linear mixed modelling, we found session effects on rest-movie functional reconfiguration efficiency in both higher order cognitive networks (executive control and default mode networks) and lower order sensory networks (visual and somatomotor networks) for 2 movies (Circus and Jones). No session effects were observed with the other movie (Inscapes) – a movie with low cognitive load developed as an alternative to resting state. Using correlation analysis, we found session-dependent relevance of network reconfiguration efficiency for recall, with mainly sensory networks involved in associations with recall for session1, both sensory and higher order networks for session2, and only higher order networks for session3. These suggest that initially, sensory perceptions of the movie are important for subsequent recall, but this becomes less important with repeated viewings. Higher order networks show the opposite pattern, suggesting that processes of memory consolidation and information processing are more behaviourally relevant with repeated viewings. These associations were mostly positive, indicating that participants who required less reconfiguration from rest to movie had better recall. Overall, our findings highlight the relevance of functional network reconfiguration in naturalistic contexts. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-180
海馬において興奮は長軸に、抑制は短軸に伝わる
Longitudinal excitation and lamellar inhibition in the hippocampus
*岡本 和樹(1,2)、小池 正人(2)、日置 寛之(1,2)
1. 順天堂大学大学院医学研究科 脳回路形態学、2. 順天堂大学医学部 神経生物学・形態学
*Kazuki Okamoto(1,2), Masato Koike(2), Hiroyuki Hioki(1,2)
1. Dept Neuroanat, Juntendo Univ Grad Sch Med, Tokyo, Japan, 2. Dept Cell Biol Neurosci, Juntendo Univ Grad Sch Med, Tokyo, Japan
Keyword: HIPPOCAMPUS, SCHAFFER COLLATERAL, PHYSIOLOGY, SYNAPSE
The hippocampus forms long structure among mammalian brain. Its classic tri-synaptic circuit, which consists of DG, CA3, and CA1 subregions, is clearly visible in a transverse slice and is maintained through the long hippocampal formation (Strange et al., 2014). Therefore, the intrinsic features of the hippocampal circuit have been studied mainly with transverse slice cutting. However, directions of tri-synaptic flow are not limited in the transverse plane: Schaffer collaterals, excitatory projection from the CA3 to the CA1, extend along the longitudinal axis (or septotemporal axis) (Amaral & Witter, 1989; Ishizuka et al., 1990). While this anatomical evidence is well known, the physiological property of the longitudinal Shaffer collaterals has not been investigated. Here, we recorded the postsynaptic responses evoked by the longitudinal fibers using whole-cell patch-clamp techniques and optogenetic stimulation. After local injection of an adeno-associated virus vector expressing channelrhodopsin-2 (ChR2) into the dorsal CA3 region, we prepared 400-µm-thick acute slices transversely. Then, we recorded optogenetically evoked excitatory and inhibitory postsynaptic currents (oEPSC and oIPSC) from the CA1 pyramidal cells in both proximal and distal slices from the virus injection site, which slices had ChR2-containing dorsal CA3 axons. We found that the oIPSC amplitudes became significantly smaller in distal slices than in proximal slices, whereas the oEPSC amplitudes did not significantly changed between slices. Furthermore, the CA1 interneurons, which mediate this feedforward inhibition, received small oEPSCs in distal slices. These results indicate that the Schaffer collaterals change their connectivity along the longitudinal axis: the collaterals connect preferentially to the CA1 pyramidal cells, not to the distal CA1 interneurons. It is surprising that our results are contrary to the lamellar hypothesis (Andersen et al., 1969), which suggests that excitatory activity travels within a series of parallel hippocampal “lamellae” (Sloviter & Lømo, 2012). Instead, the feedforward inhibition is supposed to be “lamellar.” The difference between excitatory and inhibitory circuit in the longitudinal axis may underlie some hippocampal function, such as propagation of oscillation (Patel et al., 2013). | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-181
必須アミノ酸ヒスチジンによる記憶形成と想起能力の向上
Enhancement of memory formation and retrieval by essential amino acid histidine
*川嶋 珠生(1)、樺山 音々(2)、小田切 友紀(2)、谷水 俊之(1)、石川 理絵(1)、喜田 聡(1)
1. 東京大学大学院農学生命科学研究科、2. 東京農業大学
*Tamau Kawashima(1), Nene Kabayama(2), Yuki Odagiri(2), Toshiyuki Tanimizu(1), Rie Ishikawa(1), Satoshi Kida(1)
1. University of Tokyo, 2. Tokyo University of Agriculture
Keyword: social memory, amino acid, histidine, memory improvement
Histidine (His), one of the essential amino acids, is metabolized in the brain and converted into histamine. Histamine is a neurotransmitter that controls arousal, eating, and cognitive functions in the brain, and has three types of receptors (H1, H2, and H3), each of which activates different signaling pathways. On the other hand, memory consolidation is a process to stabilize labile memory through new gene expression, generating long-term memory. To update the consolidated memory, memory retrieval functions as a key process to induce reconsolidation and extinction that enhance, maintain or weaken memory. In this current study, we examined the effects of His administration on memory formation and retrieval. In the social recognition memory task, adult mice(C57BL/6) were exposed to juvenile mice for 1.5 min every 24 hours (training and test). Social recognition memory was evaluated by a decrease in the duration of the adult mouse’s social investigation behavior during test compared to training. Intraperitoneal His administration (500 mg/kg) 30 min, 12h and 24 h before training showed no effect on social recognition memory. In contrast, this administration 2 and 6 hours prior to training improved social recognition memory compared to control group although no effects on anxiety-like behavior and locomotor activity were observed. These observations suggested that His enhances memory formation. Importantly, similar memory enhancement was observed by low concentrations of His (50 mg/kg) and oral administration. Interestingly, His administration 30 minutes, 1 and 2 hours before test improved social recognition memory, suggesting that His improves memory retrieval. To understand mechanism of enhanced memory performance by His, we examined effects of histamine receptor antagonist. Co-systemic injection of His with H2 or H1 antagonist blocks improvement of memory formation and retrieval by His, respectively, suggesting distinct mechanisms of enhancement of memory formation and retrieval by His. These observations that His promotes memory formation and retrieval suggest that His functions as “memory enhancer” that provides a convenient way to improve memory performance. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-182
前頭前野を中心とする新規食物摂食記憶の神経ネットワーク
Brain networks centered on prelimbic of mPFC for a novel food memory
*福山 雄大(1)、喜田 聡(1)
1. 東京大学大学院農学生命科学研究科
*Yudai fukuyama Fukuyama(1), Satoshi Kida(1)
1. The University of Tokyo, Tokyo, Japan
Keyword: feeding, prefrontal cortex, neophobia, food memory
Food values show feeding experience-dependent changes in life. Food values have a strong influence on food preference. Food neophobia is the avoidance or reluctance to try novel foods. This biological phenomenon suggests that formation and retrieval of episodic memory of feeding novel preferred food promote feeding behavior when that food is presented again. Therefore, we hypothesize that food neophobia is a psychological model modulating food value and try to understand mechanisms of neophobia from the view of episodic memory engrams of feeding novel food. We are first attempting to identify the neural network of the food memory engram by examining neural activity-dependent gene expression. Fasted mice were fed cheese as a novel food for 30 minutes (Training) and then again for 30 min 24 hours later (Test). Cheese intake was significantly increased during test compared to training, suggesting that the mice shows neophobia toward the novel food (cheese) during training. Expression of c-fos, a marker of activity-dependent gene expression, was measured by immunohistochemistry 60 min after training. Mice fed cheese showed a significant increase in c-fos positive cells in prelimbic region (PL) of the medial prefrontal cortex, perirhinal cortex (PRh), insular cortex (IC), hippocampal CA1 area, bed nucleus of the stria terminalis (BNST), central nucleus of the amygdala (CeA), and parasubthalamic nucleus (PSTh) compared to mice fed a normal diet. We next performed in silico analysis to evaluate the functional connectivity between brain areas based on the correlation of the number of c-Fos positive cells. Interestingly, mice fed cheese showed the formation of neural network centered on the PL and basolateral amygdala (BLA). Thus, we suggested for the first time that a food memory engram centered on the PL is formed following feeding a novel food (cheese). | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-183
ノンレム睡眠時の扁桃体－皮質入力は情動による知覚記憶固定化の促進を担う
Emotional arousal enhances perceptual memory through amygdalo-cortical input during NREM sleep
*齋藤 喜仁(1,2)、大迫 優真(1,3)、小田川 摩耶(1)、大石 康博(1)、松原 智恵(1)、森田 光洋(2)、村山 正宜(1)
1. 理化学研究所脳神経科学センター、2. 神戸大学大学院理学研究科、3. 同志社大学大学院脳科学研究科
*Yoshihito Saito(1,2), Yuma Osako(1,3), Maya Odagawa(1), Yasuhiro Oisi(1), Chie Matsubara(1), Mitsuhiro Morita(2), Masanori Murayama(1)
1. RIKEN Center for Brain Science, Saitama, Japan, 2. Graduate School of Science, Kobe University, Hyogo, Japan, 3. Graduate School of Brain Science, Doshisha University, Kyoto, Japan
Keyword: memory consolidation, amygdala, cortex, sleep
Emotional arousal is thought to enhance the memory consolidation through projections from the basolateral amygdala (BLA) to sub-/cortical regions. However, it is still unclear where and how the BLA interacts to enhance memory consolidation. Furthermore, even the question of whether rapid-eye-movement (REM) or non-REM (NREM) sleep state is essential for the enhancement of memory consolidation by emotional arousal has not been settled. By using a perceptual-emotional associative learning task, electrophysiological recording and manipulation of a BLA-cortical circuit, we report that BLA neurons not only store emotional memory, but also enhance perceptual memory through BLA inputs to cortex during NREM sleep. In the associative learning task, male mice learned the floor texture paired with a female in a cup on the floor. Male mice that had associated the floor texture with the female showed a longer retention period of the floor texture memory than mice that had not been presented to the female. We have previously reported that inputs from the secondary motor cortex (M2) to the primary somatosensory cortex (S1) play crucial roles in the texture memory consolidation. Based on the results, anatomical studies indicated a strong projection from the BLA to the M2, but weak to the S1. Immunohistological analysis of activity-dependent early gene expression revealed that the female presentation to male mice during the task activates BLA neurons. Chemogenetic inactivation of M2-projecting BLA neurons during the post-learning period impaired consolidation of the female memory. Interestingly, inactivation of this circuit did not impair texture memory, but did suppress the texture memory enhancement. Furthermore, simultaneous extracellular recording from the BLA, the M2 and the S1 revealed that the female presentation enhanced reactivations of the inter-regional cell-ensembles during NREM sleep, but not during REM sleep. Finally, optogenetic inactivation of BLA inputs in the M2 during NREM sleep suppressed the enhancement of the texture memory consolidation but not the female memory. A similar circuit-manipulation during REM sleep did not impair any behavioral parameters in our observation. These results demonstrate that BLA-M2 inputs during NREM sleep have a causal role in the enhancement of the perceptual memory consolidation by emotional arousal. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-184
Adult-born neuron activity in the establishment of fear generalization
*Jiahui Yu(1), Pablo Vergara(1), Toshie Naoi(1), Yuteng Wang(1), Yoan Cherasse(1), Takeshi Sakurai(1), Masanori Sakaguchi(1)
1. International Institute for Integrative Sleep Medicine (WPI-IIIS)
Keyword: contextual fear generalization, neurogenesis, memory consolidation, pattern separation
Overgeneralization of fear in safe contexts is considered a hallmark of post-traumatic stress disorder. Traditional behavior paradigm to analyze fear generalization requires more than ten days1, which prevents the understanding of how fear generalization establishes in a short time in parallel with memory processing, including memory consolidation. It is known that adult-born neurons (ABNs) continuously generated in the hippocampus play a key role in a contextual fear generalization by being recruited in the post-learning memory consolidation23. We previously elucidated the dynamic activity change of ABNs in REM sleep and their necessity in the memory consolidation4. However, their activity patterns in memory consolidation responsible for fear generalization are completely unknown. In this study, we first constructed a robust behavior paradigm to analyze the establishment of contextual fear generalization. We monitor overall ABN activity within a field of view across the course of fear generalization by employing calcium imaging in freely moving mice. This study provides new perspectives into understanding the mechanisms of fear generalization.
References
1. Nakashiba, T. et al. Young Dentate Granule Cells Mediate Pattern Separation, whereas Old Granule Cells Facilitate Pattern Completion. Cell 149, 188–201 (2012).
2. Arruda-Carvalho, M., Sakaguchi, M., Akers, K. G., Josselyn, S. A. & Frankland, P. W. Posttraining ablation of adult-generated neurons degrades previously acquired memories. J. Neurosci. 31, 15113–15127 (2011).
3. Sahay, A. et al. Increasing adult hippocampal neurogenesis is sufficient to improve pattern separation. Nature 472, 466–470 (2011).
4. Kumar, D. et al. Sparse Activity of Hippocampal Adult-Born Neurons during REM Sleep Is Necessary for Memory Consolidation. Neuron 107, 552-565.e10 (2020).
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3P-185
齧歯類における海馬-嗅内皮質路の投射解析
Hippocampal-entorhinal projections are differently organized between medial and lateral entorhinal cortex in rodents
*大原 慎也(1,2)、Witter Menno(1,2)、筒井 健一郎(1)
1. 東北大学大学院生命科学研究科 脳神経システム分野、2. Kavli Inst for Sys Neurosci, NTNU, Trondheim, Norway
*Shinya Ohara(1,2), Menno P Witter(1,2), Tsutsui Ken-Ichiro(1)
1. Lab of Sys Nerosci, Tohoku Univ Grad Sch of Life Sci, Sendai, Japan, 2. Kavli Inst for Sys Neurosci, NTNU, Trondheim, Norway
Keyword: entorhinal cortex, hippocampus, layer V, anterograde tracing
The entorhinal cortex (EC), a major gateway between the hippocampus (HPC) and the neocortex, is composed of two subdivisions, the medial and lateral EC (MEC and LEC). In both subdivisions, layer V neurons are considered to play a crucial role in memory consolidation by relaying HPC information to the neocortex. Previous studies have reported that EC layer V is composed of two connectionally different sublayers: a deep layer Vb (LVb) which receives HPC inputs and projects intrinsically, and a superficial layer Va (LVa) which originates the main projections out to telencephalic structures. We recently reported that the intrinsic circuits of EC layer V differ between MEC and LEC, and LVb-to-LVa connections are more prominent in LEC than in MEC (Ohara et al. eLife, 2021). This raises a question whether there are differences also in the HPC-EC projections within the two subdivisions.
Here, we systematically examined the HPC-EC projections in rats by injecting anterograde tracers into the output regions of HPC, either CA1 or subiculum, at different dorsoventral- and proximodistal-levels. In line with previous studies, HPC-EC projections were topographically organized along the proximodistal axis of HPC. Anterograde tracer injections in the proximal-CA1/distal-subiculum resulted in labeled-fibers mainly in MEC, whereas injections in the distal-CA1/proximal-subiculum resulted in labeled-fibers preferentially in LEC. The HPC-LEC projections also showed topographical patterns along the dorsoventral axis: dorsal HPC projects to dorsolateral LEC and ventral HPC project to ventromedial LEC. These HPC-LEC projections terminated both in LVb and LVa. In contrast to LEC and also to previous studies, HPC-MEC projections did not show topographical patterns along the dorsoventral axis. Although dorsal HPC targeted dorsal MEC, ventral HPC targeted not only ventral MEC but also dorsal MEC. In addition, these projections showed clear laminar preference within MEC layer V. While dorsal HPC projections mainly terminated in MEC LVb, projections from ventral HPC mainly terminated in MEC LVa. In other words, neurons in ventral HPC likely innervate the LVa neurons throughout the whole dorsoventral extent of MEC. These results show that the HPC-EC projections are differently organized between LEC and MEC and indicate that MEC outputs from LVa rely on the inputs from ventral HPC. These findings may provide new insights to unravel the neuronal basis underlying memory consolidation. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-186
前Bötzinger複合体の中枢性吸息活動に誘発される記憶固定
Memory consolidation induced by central inspiratory activity from the PreBötzinger complex
*中村 望(1)、古江 秀昌(1)、小林 憲太(2)、越久 仁敬(1)
1. 兵庫医科大学生理学生体機能部門、2. 自然科学研究機構生理学研究所ウイルスベクター開発室
*Nozomu H. Nakamura(1), Hiromasa Furue(1), Kenta Kobayashi(2), Yoshitaka Oku(1)
1. Department of Physiology, Hyogo College of Medicine, 2. Section of Viral Vector Development, National Institute of Physiological Sciences
Keyword: Respiration, Cognition
There is growing evidence that memory performance is modulated by timings of respiratory cycles. Our previous study of human behavior showed that performance accuracy was remarkably decreased when the onset of inspiration (i.e., expiratory-to-inspiratory phase transition) emerged in the middle of memory processes. To elucidate a temporal role of central inspiratory activity during memory processes, we used the optogenetic manipulation in awake mice and controlled activation of the PreBötzinger complex (PreBötC), the primary inspiratory rhythm generator in the medulla oblongata. To do so, channelrhodopsin-2 (ChR2) was expressed in PreBötC neurons of vesicular GABA transporter (Vgat)-Cre mice. During an object recognition memory task, novel object detection was impaired in the transgenic mice when intermittent apnea with a 2-sec duration, which was derived from the PreBötC, covered 67% of object exploration time during encoding. We then designed a nonobject version of a fear conditioning paradigm because object exploration in rodents may partially contain their olfactory strategies, which are closely related to breathing. Notably, the transgenic mice did not show freezing behavior during conditioned stimuli of fear (CS+) when they had short-term apnea derived from the PreBötC at the exact timing of encoding (i.e., making an association with footshocks). Immediate-early gene Arc catFISH method indicated that PreBötC-induced apnea during encoding did not alter the positive cell population in CA3 hippocampus during CS+ and conditioned inhibition (CS-) and caused more cells to co-express Arc between CS+ and CS-. Meanwhile, the positive cell population in CA3 in wild-type mice was higher during CS+ than CS-. We demonstrate that short-term apnea with sub-second time resolution induced by central inspiratory activity disrupts associative memory encoding and subsequent consolidation in CA3. These findings suggest that central inspiratory signals from the PreBötC may be required for hippocampal-dependent memory consolidation. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-187
鱗食性シクリッドPerissodus microlepisの利き獲得に必要な発達初期の経験学習
Experience dependent-learning of behavioral laterality at early developmental stage in the scale-eating cichlid Perissodus microlepis
*竹内 勇一(1)、樋口 祐那(1)、池谷 幸樹(2)、田上 正隆(2)、小田 洋一(3)
1. 富山大学、2. 世界淡水魚園水族館アクアトト・ぎふ、3. 名古屋大学
*Yuichi Takeuchi(1), Yuna Higuchi(1), Koki Ikeya(2), Masataka Tagami(2), Yoichi Oda(3)
1. university of Toyama, 2. World Freshwater Aquarium Aquatotto Gifu, 3. Nagoya University
Keyword: Laterality, Behavioral development, Learning, Predation
Although behavioral laterality has been demonstrated in a wide range of animals, its developmental bases are not well-understood. In this study, we report the developmental stage-dependent learning of laterality in foraging behavior in a scale-eating cichlid Perissodus microlepis. We used fish in three life stages (juvenile, young, and adult) with different diets to examine how behavioral laterality is developed and its association with foraging experience, morphological asymmetry, and predation kinematics and success. Our results indicate that juvenile and young fish retain the ability to learn different aspects of laterality in foraging behavior, whereas adults do not. Juvenile at just starting scale-eating strengthened not only attack side preference but also developed body flexion movement during the dominant side attack through scale-eating experience during the short periods of scale-eating experience. On the other hand, young fish did not develop the lateralized body flexion movement. Based on our findings, we suggest that P. microlepis during the early stages of development have an innate attack side preference and develop lateralized scale-eating behavior with phase-dependent learning. Taken together, the acquisition of behavioral laterality is quite similar to that of vocal communication in songbird and human that can be limited to learn at specific early stage of development (so-called "sensitive phase"). | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-189
Investigating Functions of Parallel Connections in the Zebra Finch Higher Auditory Cortex For Memory Processing During Song Learning
*Sarah Morson(1), Yuichi Morohashi(1), Yoko Yazaki-Sugiyama(1)
1. Okinawa institute of Science and Technology Graduate University
Keyword: Zebra Finch, Memory, tetON/tetOFF
Male juvenile zebra finches learn to sing by listening and memorizing, and then mimicking their tutor’s song. The caudomedial nidopallium (NCM) and caudomedial mesopallium (CMM) are the zebra finch higher auditory cortex. The NCM has been evidenced as a site of tutor song memories (Yanagihara and Yazaki-Sugiyama 2016), while the neighbouring CMM has been also reported to correlate with memory formation and directly project to the song motor area, HVC. While it has been hypothesised that the NCM and CMM may act as parallel auditory memory places for tutor song, the connections between these two regions and how the location of tutor song memory may change as birds develop their own song has yet to be understood. Here, by using newly optimised cFos TetON/TetOFF system in zebra finch, we separately labelled the neurons responding to tutor song with EGFP and the ones responding to bird’s own song with mRFP (using AAV2/9 cFos TetON-EGFP and AAV2/9 cFos TetOFF-mRFP) in both the NCM and CMM of adult male zebra finches. Anatomical analysis has revealed the distinct neuronal populations which were activated by either tutor song, bird’s own song, or both in both the NCM and CMM. These populations do not differ in their proportions between the adult NCM and CMM (n=3 birds, p>0.005) implying that they are represented equally in both regions in adult male birds. We are also performing tracing analysis of tutor responsive neurons in the NCM which have shown projections to the CMM region and those in the CMM project to the NCM. More detailed analysis by labelling tutor responsive cells with EGFP in the NCM and mRFP in the CMM have provisionally shown that tutor song responsive neurons in the NCM and CMM project to each other suggesting an important interaction between these two regions in storage of tutor song memory. Those suggest that both the NCM and CMM involve neuronal substrates of tutor song memory, and they are interacting with each other. The further analysis allow us to see how these tutor response neurons in two brain sites interact with each other. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-190
ショウジョウバエ成虫脳におけるドーパミン受容体とドーパミントランスポーターの局在
Localization of dopamine receptors and dopamine transporter in adult Drosophila brain.
*松野 元美(1)、宮下 知之(1)、今野 幸太郎(2)、三上 恭平(1)、堀内 純ニ郎(1)、渡辺 雅彦(2)、齊藤 実(1)
1. 公益財団法人 東京都医学総合研究所、2. 北海道大学大学院医学研究科 解剖学講座 解剖発生学分野
*Motomi Matsuno(1), Tomoyuki Miyashita(1), Kotaro Konno(2), Kyohei Mikami(1), Junjiro Horiuchi(1), Masahiko Watanabe(2), Minoru Saitoe(1)
1. Tokyo Metropolitan Institute of Medical Science, 2. Department of Anatomy, Faculty of Medicine, Hokkaido University
Keyword: Drosophila, dopamine receptor, immunohistochemistory
Flies can be trained to learn and remember both aversive and appetitive cues. Most studies agree that dopamine (DA) is necessary for acquisition of both these aversive and appetitive memory. Upon secretion, DA binds to receptors on postsynaptic cells and modulates intracellular signaling cascades. Drosophila express D1-like dopamine receptor, Dop1R1, which stimulate adenylyl cyclase via the Gs subunit, D2-like dopamine receptor, Dop2R, which is Gi-coupled DA signaling, and invertebrate-specific receptor, Dop1R2, which is Gq-coupled DA signaling. Therefore, the effect of DA on a specific postsynaptic neuron depends on the type of DA receptor that is expressed. Identification of precise each receptor localization in detail on specific neurons is expected to help towards better understanding of their function during memory formation. However, since there is little histochemical observation about these receptors and transporter, it is unclear the precise cellular localization in mushroom body (MB) neurons, the major site of associative odor memory formation, or in its synapses in adult brain. In this study, we generated polyclonal antibody against Dop1R1, Dop1R2, Dop2R and DAT, and found that different type of dopamine receptors and DAT were co-expressed in specific expression level on each compartment of MB neurons. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-191
卵白に由来する認知機能改善作用を持つ新規ペプチドの発見
A novel peptide derived from egg white improved cognitive decline in mice
*中島 尚信(1)、正箱 麻衣子(1)、金子 賢太郎(1)、井上 和生(1)、大日向 耕作(1)
1. 京都大学大学院農学研究科
*Takanobu Nakajima(1), Maiko Shobako(1), Kentaro Kaneko(1), Kazuo Inoue(1), Kousaku Ohinata(1)
1. Grad Sch Agr, Kyoto-University, Kyoto, Japan
Keyword: COGNITIVE FUNCTION, BIOACTIVE PEPTIDE, EGG
A number of bioactive peptides have been found in enzymatic digests of natural food proteins. Egg (Gallus gallus domesticus) is one of the most important resources of protein, and it is essential food because of its accessibility and favorable features that can be obtained by processing.
Dementia is a disease that affects many people worldwide and is a major concern for the extension of the healthy life expectancy. As egg intake was reported to be positively correlated with cognitive function, we focused on eggs. In this study, we found that the enzymatic digest of egg white protein, a major egg protein source, improves cognitive decline after oral administration in mice.
To measure cognitive function, we conducted the object recognition test (ORT). Mice were fed a high fat diet (HFD) for 7 days, which we previously demonstrated reduces cognitive function [1]. Ovalbumin, a major protein of egg white, was digested by the protease thermolysin. Orally administered thermolysin digest increased the approach time to the new objects in the ORT, suggesting that the digest improved cognitive decline induced by HFD.
Next, we searched for peptides with the potential to improve cognitive decline in mice fed HFD. ILPEY, a novel pentapeptide in the digest, increased the approach time to new objects, suggesting that it improved cognitive decline. To examine whether the improvement in cognitive function by ILPEY is mediated by the acetylcholine system, we used an α7 nicotinic acetylcholine receptor (α7nAChR) antagonist, methyllycaconitine. The effects of ILPEY were blocked by the antagonist, suggesting that ILPEY improves cognitive decline via the acetylcholine system.
In conclusion, the novel peptide ILPEY from thermolysin-digested ovalbumin improved cognitive decline in mice fed a HFD via α7nAChR. This is the first report of an egg peptide that improves cognitive decline.
1. Nagai et al. FASEB J., 2019, 33(12),14095-14102. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-192
味覚嫌悪学習の想起時における条件刺激の摂取と接近は扁桃体中心核ニューロンの化学遺伝学的活性化によって増加する
Licking and approaching a conditioned aversive taste stimulus are increased by chemogenetic activation of the central amygdala neurons
*乾 賢(1)、菊池 媛美(2)、舩橋 誠(1)
1. 北海道大学 大学院歯学研究院 口腔生理学教室、2. 北海道大学 大学院歯学研究院 歯科矯正学教室
*Tadashi Inui(1), Emi Kikuchi(2), Makoto Funahashi(1)
1. Department of Oral Physiology, Graduate School of Dental Medicine, Hokkaido University, 2. Department of Orthodontics, Division of Dental Medicine, Graduate School of Dental Medicine, Hokkaido University
Keyword: conditioned taste aversion, retrieval, CeA, DREADD
Conditioned taste aversion (CTA) decreases the taste palatability of a conditioned stimulus (CS) and produces fear for approaching the CS. The decreased palatability and fear suppress the intake of the CS during the retrieval of CTA. To explore the role of the central amygdala (CeA) in the behavioral responses to a learned aversive CS during CTA retrieval, here we examined the effect of chemogenetic activation of the CeA neurons on ingestive and approaching behavior to the CS in conditioned mice. An adeno-associated virus vector (AAV8-hSyn-hM3Dq-mCherry) was bilaterally injected into the CeA (0.3 µl/side) of male C57/BL6 mice. After the surgery, the mice received a pairing of a 0.2% saccharin solution (CS) and an i.p. administration of a 0.3 M lithium chloride (US). The conditioned mice were exposed to the CS in Test 1 to assess the robustness of the CTA. Based on the intake of the CS, the mice were divided into two groups: experimental and control. The experimental group was intraperitoneally administered with a designer drug deschloroclozapine (DCZ, 50 µg/kg, 0.5% B.W.) ninety minutes before the CS presentation in Test 2. In contrast, the control group received vehicle injection (1% DMSO in saline, 0.5% B.W.). The behavioral experiments were performed in a chamber to analyze the mice’s licks and accesses to a spout containing the CS. The administration of DCZ significantly increased the consumption of the CS (p < 0.05) and the size of burst (persistent licking with less than 1-sec inter-lick interval) (p < 0.05), compared to the vehicle administration. Since a larger burst size means higher taste palatability, the DCZ likely attenuated distaste for the CS, resulting in increased consumption. The approaching behaviors were categorized as Entry-Lick and Entry-Stop. The former is an event in which mice approached the spout and then licked it at least once, and the latter is in which mice approached but not licked. The DCZ administration significantly augmented the total duration of both Entry-Lick and Entry-Stop (p < 0.05, respectively). These results imply that approaching behavior for the CS was increased by the stimulation of hM3Dq-expressing cells in the CeA. Therefore, it is suggested that the CeA neurons are involved in decreased taste palatability and suppressed approaches for a CS during the retrieval of CTA. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-193
内因性オキシトシンは物体認識能を調節している
Endogenous oxytocin modulates object recognition memory
*高橋 純平(1)、山田 大輔(1)、佐野 良威(2)、古市 貞一(2)、斎藤 顕宜(1)
1. 東京理科大学大学院薬学研究科 薬理学研究室、2. 東京理科大学大学院理工学研究科 分子神経科学研究室
*Junpei Takahashi(1), Daisuke Yamada(1), Yoshitake Sano(2), Teiichi Furuichi(2), Akiyoshi Saitoh(1)
1. Lab Pharmacol, Fac Pham Sci, Tokyo Univ of Sci, 2. Lab Mol Neurosci, Fac Sci and Tech, Tokyo Univ of Sci
Keyword: Endogenous oxytocin, Hippocampus, Memory, Supramammillary nucleus
【Introduction】Oxytocin (OXT) is a peptide hormone produced in the paraventricular nucleus of the hypothalamus (PVN), where OXT neurons project to various brain regions and its receptor expression is widely distributed. Although it has been reported that administration of OXT affects cognitive function, it is unclear how endogenous OXT plays a role in cognitive function. In the present study, we aimed to elucidate the role of endogenous OXT in cognitive function. 【Materials & Methods】AAV8-hSyn-DIO-hM3Dq-mCherry was injected to the PVN of OXT-iCre mice (C57BL/6-Oxttm1.1(Cre)Ksak) to express hM3Dq, an excitatory DREADD, specifically in OXT neurons. M3Dq agonist, clozapine-N-oxide (CNO), was intraperitoneally administered to specifically activate OXT neurons. We also mated OXT-iCre mice with mice floxed with CAPS2 (C57BL/6-Cadps2tm1.1Ksak), which is involved in neurotransmitter release, to produce mice lacking CAPS2 only in OXT neurons (CAPS2 cKO mice). Object recognition memory was assessed with the novel object recognition task (NORT). In addition, we observed the expression of mCherry and c-Fos by immunohistochemical staining to confirm the projection area of OXT neurons and neuronal activity, respectively. 【Results】In NORT, the percentage of exploration time of novel object was significantly increased in the CNO-treated mice with specific activation of OXT neurons. On the other hand, the percentage of exploration time of novel object was significantly decreased in NORT in CAPS2 cKO mice. The CNO-treated mice showed a significant increase in the number of c-Fos-positive cells in the hippocampal dentate gyrus (DG) and supramammillary nucleus (SuM). The mCherry-positive axons in OXT-iCre mice were identified in the hippocampus and SuM. 【Discussion】These results suggested that specific activation of OXT neurons improves object recognition memory, whereas the decreased OXT secretion impairs object recognition memory, and that OXT neurons in PVN projected to the DG and SuM could be involved in the enhancement of object recognition memory. On the other hand, the percentage of exploration time of novel object was significantly decreased in NORT in CAPS2 cKO mice, suggesting that decreased OXT secretion impairs object recognition memory. Taken together, we proposed that object recognition memory in mice could be modulated by the endogenous OXT neurons in PVN projecting to the DG and SuM. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-194
RNA修飾N6-メチルアデノシン結合タンパク質YTHDF3ノックアウトマウスの行動解析
Behavioral analysis on RNA modification N6-methyladenosine (m(6)A) binding protein YTHDF3 neuronal knockout mice
*助川 桃枝(1,2)、Hou Shengqun(1,2)、吉原 亨(3)、王 丹(1,2)
1. 京都大学生命科学研究科、2. 理化学研究所生命機能科学研究センター、3. 京都大学大学院医学研究科附属動物実験施設
*Momoe Sukegawa(1,2), Shengqun Hou(1,2), Toru Yoshihara(3), Dan Ohtan Wang(1,2)
1. Graduate School of Biostudies, Kyoto University, Kyoto, Japan, 2. RIKEN Center for Biosystems Dynamics Research, Kobe, Japan, 3. Institute of Laboratory Animals, Graduate School of Medicine, Kyoto University, Japan
Keyword: RNA modification, enriched environment, gene-environment interaction
Environmental factors and genetic backgrounds have been shown to impact individuals’ development of cognitive and emotional functions in an intertwined manner. The molecular mechanisms underpinning such gene-environment interactions are imperative to understand but remain largely elusive. To explore potential underlying epitranscriptomic pathways, we subjected neuronal YTHDF3 conditional KO mice (YTHDF3, a cytoplasmic reader protein for N6-methyl-adenosine of RNAs) to an enriched housing environment (EE). EE has been demonstrated to provoke overall behavioral benefits albeit diverse responses in different mouse strains. In C57BL/6 mice, anatomical and epigenetic changes associating with synaptic plasticity and neurogenesis have been shown in cortical and hippocampal excitatory neurons that require de novo transcription and translation. In addition to the recent finding associating YTHDF3 mono-allelic loss with intellectual and developmental disorders in humans, we previously observed synaptic deficits in YTHDF3-knockdown cultured rodent hippocampal neurons. To further explore the physiological function of YTHDF3, we housed YTHDF3 conditional knockout mice (CaMKIIa-Cre: to specifically inactivate YTHDF3 in mature forebrain excitatory neurons) in EE between 8-13 postnatal weeks and performed behavioral tests. In cKO animals, we observed a stronger grip strength and decreased sociability. EE induced behavioral changes such as enhanced motor skills and auditory sensitivity, reduced anxiety-like behavior, and facilitated social behavior. These effects were detected in both cWT and cKO mice; and no statistically significant genotype environment interaction was detected in this test battery (significance level p = 0.05). Possibly, our results represent part of the YTHDF3 deficiency-driven behavioral alterations in the model animals and suggest distinct roles of epitranscriptomic and epigenetic regulation. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-195
時計ニューロンLNdから放出される神経伝達物質は長期記憶に必須である
Long-term memory is modulated by transmitter release from dorsal-lateral clock neurons
*倉田 裕斗(1)、鈴木 悠希(1)、坂井 貴臣(1)
1. 東京都立大学
*Yuto Kurata(1), Yuki Suzuki(1), Takaomi Sakai(1)
1. Tokyo Metropolitan University
Keyword: Drosophila melanogaster, memory, clock neuron, courtship
In nature, animals acquire memory from various learning experiences. A newly formed memory is initially labile. However, it is consolidated in the brain neurons under certain conditions, and consolidated memory is maintained for a long time. The fruitfly Drosophila melanogaster is an excellent model to elucidate the molecular and cellular mechanisms of learning and memory because genetic tools to modify gene expression and neural function are available. One of the behavioral assays to measure Drosophila memory, courtship conditioning, has been used to investigate molecular mechanisms of Drosophila LTM. In this assay, virgin males receive stressors (e.g., courtship-inhibiting cues and sexual rejection) from previously mated females, thereby interfering with mating success. After conditioning, their memory is observed as courtship suppression even toward virgin females. We previously reported that the circadian clock gene period (per) gene is essential for consolidating courtship LTM. Per is expressed in 150 neurons in the adult Drosophila brain (clock neurons). We have recently found that disruption of synaptic transmission from a subset of per-expressing dorsal-lateral clock neurons (LNds) impairs LTM maintenance. This result indicates that neurotransmitter release from LNds is involved in LTM maintenance. It is already known that several neurotransmitter-related genes are expressed in LNds [e.g., Tyrosine decarboxylase 2 (Tdc2), Tyramine β hydroxylase (Tbh), Choline acetyltransferase (ChAT), Vesicular acetylcholine transporter (VAChT), and neuropeptide F (NPF)]. Thus, the release of octopmine, acetylcholine. or NPF from LNds may play a key role in LTM maintenance. Our current study revealed that LNd-specific knockdow of Tdc2, Tbh, and NPF impairs courtship LTM. Thus, we will show whether these transmitters are necessary for memory consolidation, maintenance, or retrieval. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-196
ドーパミンD1受容体を介した神経伝達は、文脈的恐怖条件付けの遠隔記憶を促進する
Dopamine D1 receptor mediated neurotransmission facilitates remote memory of contextual fear conditioning
*齊藤 奈英(1)、板倉 誠(2)、笹岡 俊邦(1)
1. 新潟大学 脳研究所、2. 北里大学医学部
*Nae Saito(1), Makoto Itakura(2), Toshikuni Sasaoka(1)
1. Brain Research Institute, Niigata Univ, Niigata, Japan, 2. Kitasato Univ Sch of Med, Sagamihara, Japan
Keyword: D1 receptor, Aversive learning, Remote memory
Dopaminergic neurotransmission via dopamine D1 receptors (D1Rs) is considered to play an important role not only in reward-based learning but also in aversive learning. The contextual and auditory cued fear conditioning tests involve the processing of classical fear conditioning and evaluates aversive learning memory. It is possible to evaluate aversive learning memory in two different types of neural transmission circuits. In addition, when evaluating the role of dopaminergic neurotransmission via D1R, to avoid the effects in D1R-mediated neural circuitry alterations during development, it is important to examine using mice in which D1R expression in the mature stage is suppressed. We investigated the role of dopaminergic neurotransmission via D1Rs in aversive memory formation in contextual and auditory cued fear conditioning tests using D1R knockdown (KD) mice, in which the expression of D1Rs could be conditionally and reversibly controlled with doxycycline (Dox) treatment. For aversive memory, we examined memory formation using recent memory one day after conditioning, and remote memory four weeks after conditioning. Furthermore, immunostaining of the brain tissues of D1RKD mice was performed after two patterns of aversive footshock stimulation using fear conditioning and passive avoidance device, to investigate the distribution of activated c-Fos, an immediate-early gene. Activated c-Fos was observed in the hippocampus, striatum, amygdala, and prefrontal cortex during aversive memory formation. Next, immunoblotting was performed using hippocampal, striatal, and amygdala samples from D1RKD mice to investigate the increase in the amount of c-Fos and phosphorylated SNAP-25 at Ser187 residue. When D1R expression was suppressed using Dox, behavioral experiments revealed that impaired contextual fear learning in remote aversion memory following footshock stimulation. This is consistent with the fact that the expression of c-Fos in the hippocampus and striatum, and its upregulation by footshock stimulation, is reversible, and that it is reduced in the D1R-mediated neurotransmission-deficient state and becomes comparable to that in control mice when D1R-mediated neurotransmission is restored. In addition, although it was predicted that the amount of SNAP-25 phosphorylation would decrease, similar to that of c-Fos due to D1R suppression it was found that SNAP-25 phosphorylation was unexpectedly elevated following D1R suppression compared to that in WT mice. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-197
空間・オブジェクト記憶における内側外側嗅内皮質の役割
The Role of the Medial and Lateral Entorhinal Cortex in Place and Object Fear Memory
*荒井 翔子(1)、Krzysztof Andrzej Sypniewski(1)、Constantine Pavlides(1)
1. 筑波大学大学院人間総合科学研究科
*Shoko Arai(1), Krzysztof Andrzej Sypniewski(1), Constantine Pavlides(1)
1. Grad Sch Comprehensive Human Sci, Univ of Tsukuba, Ibaraki, Japan
Keyword: ENTORHINAL CORTEX, OBJECT MEMORY, SPATIAL MEMORY, FEAR CONDITIONING
Based mainly on unit recording and lesion studies, the entorhinal cortex (EC) has been functionally subdivided into medial (MEC) and lateral (LEC) parts. The MEC is said to process information about space while the LEC processes information about objects. To more precisely determine a functional dissociation of EC sub-regions in episodic memory, we optogenetically inhibited the MEC/LEC during the training phase of a fear conditioning task which included either spatial or object information. An adeno-associated virus expressing NpHR3.0 or GFP (control) was injected and optic fibers were implanted to inhibit MEC/LEC of Long-Evans rats. Inhibition was validated by unit recordings during fiber implantation and the virus-infected area was verified histologically. For spatial memory, animals were fear conditioned (0.3mA or 1mA foot shocks) on one of the arms of an elevated plus maze while inhibiting MEC. For object memory, animals were fear conditioned (1mA) on an elevated plus maze when they touched an object located at the end of a specific arm, while inhibiting LEC. A no-shock control object was placed on a different arm. 24h later, the animals’ memory of place or object were tested by scoring avoidance (time spent on each arm and food retrieval) towards arms and objects. Repeated measures two-way ANOVA followed by post-hoc Sidak’s test was performed for between and within group comparisons. Preliminary data show that avoidance toward the shock arm of MEC inhibited animals (n=2) was comparatively lower than controls (n=6) when weak shocks (0.3mA) were delivered in the training. In strong foot-shock condition (1mA), MEC inhibited animals (n=6) avoided the shock arm longer than no-shock arms (p < 0.05). Also, they tended to avoid adjacent arms more, compared to the distant arm (p = 0.06). In control group (n=9), 5/9 animals avoided every arm completely while the others avoided the shock arm longer (p < 0.01) than no-shock arms. LEC inhibited (n=7) as well as control (n=5) animals showed over 90% avoidance toward shock object, however, LEC inhibited animals avoided not only the shock but also no-shock object significantly more (p < 0.05). Control animals avoided only shock object longer than other arms (p < 0.01). Thus, LEC suppression affected avoidance toward both shock and no-shock objects. These results suggest that EC sub-regions process information about specific place/object and associate this information as one context. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-198
ショウジョウバエのドーパミンニューロン由来のセカンドトランスミッターは嗅覚記憶の安定化を制御する
Second transmitters from dopamine neurons have specific roles in olfactory memory maintenance in Drosophila
*山﨑 大介(1)、前山 有子(1)、多羽田 哲也(1)
1. 東京大学定量生命科学研究所
*Daisuke Yamazaki(1), Yuko Maeyama(1), Tetsuya Tabata(1)
1. Inst Quant Biosci, Univ of Tokyo, Tokyo, Japan
Keyword: forgetting, dopamine, Drosophila, memory
Memory maintenance is one of the important physiological events for survival of animals. In Drosophila memory maintenance would be processed in the mushroom, an olfactory memory center where olfactory and valence information are merged. Olfactory inputs are transferred from olfactory receptor neurons in the anntena mediated by projection neurons to the mushroom body. Valence inputs are delivered to the mushroom body through two major dopaminergic cluster neurons, PAM and PPL1. Each neuron extends axons to the different compartments onto the mushroom body axons. Prior works have shown that PPL1 dopaminergic inputs mediated by D1-like receptor are responsible for aversive memory forgetting in Drosophila. Furthermore, activation of PPL1 neurons after aversive learning disrupts memory maintenance. However, it was unknown about which of the axon compartments or the neuron populations of mushroom body Kenyon cells are responsible for forgetting. In this study we demonstrate that activities of PAM and PPL1 neurons after learning had important roles in appetitive and aversive memory forgetting, respectively. We also show that inhibitory second transmitters from each dopaminergic cluster played specific functions on each valence memory. Inhibition of glutamate transporter by RNAi in PPL1 neurons enhanced aversive memory retention and generated long-lasting memory by single cycle trainining. Similarly inhibition of GABA synthesis in PAM neurons potentiated appetitive memory consolidation. Notably these facilitated memory were not interfered wth the activation of dopaminergic neurons. Finally we also found that second transmitters from PAM and PPL1 could be processed by specific subclasses of the mushroom body γ neurons, γCRE-n and γCRE-p neurons, respectively. These results suggest that appetitive and aversive memory maintenance could be processed through different molecular pathways and circuits without interferences. In Drosophila, olfactory memory can be represented as the plastic depression of the connection between Kenyon cells and output neurons (MBONs). Therefore our findings of inhibitory transmission may be a key to explain this mechanism. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-199
前頭前野における恐怖と消去を制御するニューロン集団
Neuronal population regulating fear and extinction in mPFC
*石川 理絵(1)、喜田 聡(1)
1. 東京大学大学院農学生命科学研究科
*Rie Ishikawa(1), Satoshi Kida(1)
1. Grad Sch Agr, Univ of Tokyo, Tokyo, Japan
Keyword: fear memory, reconsolidation, extinction, mPFC
Brief fear memory retrieval triggers fear responses, then inducing memory reconsolidation, whereas long-time or repeated retrieval extinguishes fear memory. Memory circuits expressing fear and its extinction have been identified, respectively. However, discrimination and interaction of fear and extinction neurons have not well examined. We have identified and characterized “fear” and “extinction” neuron using contextual fear conditioning and inhibitory avoidance (IA) tasks. We found that c-fos positive neurons are increased in the mPFC, hippocampus and amygdala when fear memory is reconsolidated, while these neurons are increased in the mPFC and amygdala when the memory is extinguished (Suzuki et al., 2004; Mamiya et al., 2009; Fukushima et al., 2014). In this study, we identified fear and extinction neurons using catFISH by detecting Arc and Homer1a mRNAs following retrieval of IA memory. Amygdala showed distinct neuronal populations that were activated at the reconsolidation and extinction phases, whereas mPFC showed single neuronal population that was activated at both reconsolidation and extinction phases. To further examine functional roles of this neuronal population in the mPFC, we characterized IA memory engram neurons in the mPFC using c-fos-tag system. We first labeled mPFC neurons activated when memory is reconsolidated (through the re-exposure to the light box only) by channelrhodopsin-2 (ChR2). Optogenetic activation (light on) of mPFC labeled neurons enhanced fear response compared to the control (light off), suggesting that these mPFC engram neurons function as “fear neuron”. We next labeled mPFC neuron by ChR2 activated when memory is extinguished (through the re-exposure to the dark box). In contrast to results as above, optogenetic activation of these neurons weakened fear responses compared to the control (light off), suggesting that mPFC engram neurons function as “extinction neurons”. These results suggest that mPFC shows single neuronal population regulating memory reconsolidation and extinction. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-200
海馬ー皮質間の協調活動は動物の状態に依存し飼育環境によって影響を受ける
Brain state-dependent cortico-hippocampal network dynamics are modulated by postnatal stimuli
*篠原 良章(1)、纐纈 真之介(2)、平瀬 肇(3)、Takatoshi Ueki(2)
1. 自治医科大学、2. 名古屋市立大学、3. コペンハーゲン大学
*Yoshiaki Shinohara(1), Shinnosuke Koketsu(2), Hajime Hirase(3), Takatoshi Ueki(2)
1. Jichi Medical University, 2. Nagoya City University, 3. University of Copenhagen
Keyword: hippocampus, cerebral cortex, sharp wave and ripples, theta
Neurons in the cerebral cortex and hippocampus discharge synchronously in a brain state-dependent manner to transfer information. Published studies have highlighted the temporal coordination of neuronal activities between the hippocampus and a neocortical area, however, how the spatial extent of neocortical activity relates to hippocampal activity remains largely unknown. We imaged macroscopic neocortical activity while recording hippocampal local field potentials in unanesthetized GCaMP-expressing transgenic mice. We found that neocortical activity elevates before and after hippocampal sharp wave ripples (SWR). SWR-associated neocortical activities occurred predominantly in vision-related regions including visual, retrosplenial and prefrontal cortex. While pre-SWR cortical activities were frequently observed in awake and sleep states, post-SWR cortical activity decreased significantly in sleep. During hippocampal theta oscillation states, phase-locked oscillations of calcium activity was observed throughout the entire neocortical state. Environmental effects on cortico-hippocampal dynamics were also assessed by comparing mice reared in an enriched environment (ENR) or under isolated conditions (ISO). In both SWR and theta oscillations, mice reared in an isolated condition exhibited clearer brain state-dependent dynamics than those reared in an enriched environment. Our data demonstrate that the neocortex and hippocampus exhibit heterogeneous activity patterns that characterize brain states, and postnatal experience plays a significant role in modulating these patterns. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-201
予測的視運動性眼球運動の獲得が前庭動眼反射の予測能にもたらす影響
The effects of acquired predictive optokinetic response on vestibulo-ocular reflex predictability in goldfish
*山中 都史美(1)、ロバート ベイカー(2)、平田 豊(1,3,4)
1. 中部大学大学院工学研究科、2. Dept. Neurosci. & Physiol., NYU Grossman Sch. Med., New York, US、3. 中部大学AI数理データサイエンスセンター、4. 中部大学創発学術院
*Toshimi Yamanaka(1), Robert Baker(2), Yutaka Hirata(1,3,4)
1. Grad. Sch. Eng., Chubu Univ., Kasugai, Japan, 2. Dept. Neurosci. & Physiol., NYU Grossman Sch. Med., New York, US, 3. Ctr. Math. Sci. & AI, Chubu Univ., Kasugai, Japan, 4. Acad. Emerg. Sci., Chubu Univ., Kasugai, Japan
Keyword: eye movement, prediction, motor learning, cerebellum
The optokinetic response (OKR) is induced reflexively by a large visual field motion to stabilize retinal image. Predictive (p)OKR was found to be acquired by goldfish after prolonged exposure to temporally periodic visual stimulation (VS) (Marsh & Baker, 1997). A recent study demonstrated that the cerebellum is required for the acquisition of pOKR (Miki et al., 2018). However, despite having identical basic vestibular and cerebellar neural circuitry to goldfish including carp, zebrafish and medaka barely exhibited pOKR (Miki et al., 2020). It was also found that all animals that acquired pOKR presented robust optokinetic after nystagmus which is considered as a manifestation of the velocity storage mechanism (VSM). Therefore, the VSM was hypothesized to be an essential determinant for the acquisition of pOKR (Miki et al., 2020). The VSM has been shown to be shared with the vestibulo-oculomotor response (VOR), another reflexive eye movement that counter-rotates the eyes in the orbit in response to head motion to suppress image slip on the retina. Both gains of the VOR (eye vel. / head vel.) and OKR (eye vel. / VS vel.) have been demonstrated to be under cerebellar control and mutually influenced. Taken together, VOR should become predictive after acquisition of pOKR. Thus, we evaluated the VOR (bilateral vel. square wave head rotation, period T=16 sec) after 3 hours of pOKR training (bilateral vel. square wave VS, T=8 sec) in goldfish under four conditions: in dark (VORd), in light w/ stationary VS (VORl), enhancement w/ opposite directional VS (VORe), and suppression w/ same directional VS (VORs). We found that VORl and VORe showed predictive decreases in eye velocity in response to extended period stimulations (T=16 sec) as both behaviors are considered to reflect pOKR components. In addition, VORd also became predictive (pVOR) although no OKR component was induced in the dark. By contrast, VORs showed no change after the acquisition of pOKR. Next, we trained goldfish in the dark for 3 hours by prolonged periodic head rotation (VORd, T=4 sec), and tested with extended period head rotation (T=8 sec). In this paradigm the VORd did not show any predictability, suggesting that acquisition of a pVOR is not possible without a visual error signal (retinal slip) that in turn drives cerebellar synaptic plasticity. Collectively these results strongly suggest that transfer of a pOKR to a pVOR occurs by sharing the same VSM-cerebellar neural loop(s). | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-202
Deep brain stimulation in the medial septum attenuates temporal lobe epilepsy via entrainment of hippocampal theta rhythm
*Ying Wang(1)
1. Qingdao University
Keyword: temporal lobe epilepsy, cognitive impairment, deep brain stimulation, medial septum
Temporal lobe epilepsy (TLE), often associated with cognitive impairment, is one of the most common types of medically refractory epilepsy. Deep brain stimulation (DBS) shows considerable promise for the treatment of TLE. However, the optimal stimulation targets and parameters of DBS to control seizures and related cognitive impairment are still not fully illustrated. In the present study, we evaluated the therapeutic potential of DBS in the medial septum (MS) on seizures and cognitive function in mouse acute and chronic epilepsy models. We found that DBS in the MS alleviated the severity of seizure activities in both kainic acid-induced acute seizure model and hippocampal-kindled epilepsy model. DBS showed antiseizure effects with a wide window of effective stimulation frequencies. The antiseizure effects of DBS were mediated by the hippocampal theta rhythm, as atropine, which reversed the DBS-induced augmentation of the hippocampal theta oscillation, abolished the antiseizure effects of DBS. Further, in the kainic acid-induced chronic TLE model, DBS in the MS not only reduced spontaneous seizures, but also improved behavioral performance in novel object recognition. Therefore, DBS in the MS is a promising approach to attenuate TLE probably through entrainment of the hippocampal theta rhythm, which may be therapeutically significant for refractory TLE treatment. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-203
ストレス誘発性の性機能障害のショウジョウバエモデルの確立
Establishment of a Drosophila model of stress-induced sexual disfunction.
*佐藤 智士(1)、坂井 貴臣(1)
1. 東京都立大学
*Tomohito Sato(1), Takaomi Sakai(1)
1. Tokyo Metropolitan University
Keyword: Drosophila, Courtship, Stress, Behavioral plasticity
Strong stress affects various cognitive behaviors after the experience. As one of the after-effects, some clinical studies have pointed out the relationship between overstress and sexual dysfunction. For example, Post Traumatic Stress Disorder (PTSD) patients are at higher risk of sexual dysfunction, including a decline in sexual motivation. Some rodent studies have reported that male rats also reduce sexual motivation after stress exposure (electrical shocks and enemy smell). However, the neural basis of stress-induced reduction in sexual motivation still remains unclear. Recently, we found that the fruitfly Drosophila melanogaster also reduces sexual motivation after exposure to stress. We confirmed that two types of stressors induce plastic courtship suppression. One is shaking stress which male flies are shaken by the laboratory shaker, and the other is restraint stress which a male fly is placed in a tiny hole (3 mm diameter and 2 mm depth). After both manipulations, the male flies reduced courtship activity, and their courtship suppression was maintained for at least one hour. Moreover, our preliminary experiments revealed that dopamine and cAMP signaling is involved in this stress-dependent courtship suppression. Genetic mutations of dopamine receptors or the rutabaga gene, which encodes adenylate cyclase, did not induce plastic courtship suppression after exposure to stress. The relevance of dopamine/cAMP signaling and stress exposure has been indicated in mammals and flies. Therefore, molecular and cellular mechanisms of stress-dependent reduction of sexual motivation may be shared in mammals and flies. In this study, we will show the critical dopaminergic neurons responsible for stress-induced courtship suppression. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-204
入力周波数に依存した海馬顆粒細胞の応答特性と情報統合
Response characteristics and information integration of hippocampal granule cells depending on input frequency
*中島 直樹(1)、篠原 颯哉(1)、早川 博章(3)、上條 中庸(2)、相原 威(1)
1. 玉川大学大学院工学研究科、2. 琉球大学大学院医学部、3. 玉川大学工学部
*Naoki Nakajima(1), Soya Shinohara(1), Hirofumi Hayakawa(3), Tadanobu Kamijo(2), Takeshi Aihara(1)
1. Grad Sch Eng, Tamagawa Univ, Tokyo, Japan, 2. Grad Sch Med, Univ of the Ryukyus, Okinawa, Japan, 3. Fac of Eng, Tamagawa Univ, Tokyo, Japan
Keyword: Hippocampus, Granule cell, Information integration, NEURON simulator
Spatial information (place) and non-spatial information (such as odor) independently propagated through the Entorhinal cortex (EC) to the hippocampal granule cells (GCs). The medial dendrite (MD) of GCs are received through the medial perforant path (MPP). The distal dendrite (DD) of GCs are received through the lateral perforant path (LPP). However, it is not clear how information though two pass ways are integrated in the GCs. In this study, to investigate the association of inputs for MD and DD.
First, in physiological experiment, to investigate the differences in response characteristics between MD and DD for regular inputs, electrical 10 pulses at 10-40 Hz of frequency were applied to MPP and LPP at in rat hippocampal slices, respectively. In our experiment, NMDA receptor was blocked by D-AP5 (NMDA receptor antagonist) to avoid the induction of synaptic plasticity. The inhibition by GABAA receptor was blocked by picrotoxin (GABAA receptor antagonist). As the result, EPSPs (excitatory post-synaptic potential) for successive input pulses in MD were transiently decreased as the number of inputs increased with and without inhibitory inputs. On the other hand, EPSPs in DD showed sustained responses to 10-30 Hz. However, responses of DD did not show those sustained responses without inhibitory inputs. Moreover, after synaptic plasticity occurred by applied tetanus stimuli (100Hz, 100pulses) without D-AP5, the response characteristics of MD were measured at 10-40 Hz of input frequency. As the result, responses of MD were also transiently decreased as in the case of naïve without induction of synaptic plasticity. The result suggest that the characteristics of information processing was kept, even the efficacy of synaptic transmission was enhanced by inducing synaptic plasticity.
Next, computer simulation was performed using a model of the GC by using NUERON simulator. The model was fixed by parameter fitting for our physiological experimental data. Theta burst (8Hz) and random pulse input (10-40 Hz) applied MD and DD, respectively. As the result, the temporal-pattern sensitivity for burst inputs to MD was enhanced when 20 Hz random pulse input was applied to DD. However, 10 Hz, 30Hz and 40 Hz random pulse inputs were simultaneously applied to DD, temporal pattern sensitivity for theta burst at MD was broad. Our result suggest that temporal-pattern discrimination of spatial information was enhanced by non-spatial information at 20 Hz in GCs. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-205
海馬シナプス後肥厚部タンパク質BEGAINの海馬依存的な記憶形成への関与
Involvement of BEGAIN in memory formation as an excitatory postsynaptic protein in the hippocampus
*片野 泰代(1)、今野 幸太郎(2)、高雄 啓三(3)、阿部 学(4)、崎村 建司(4)、宮川 剛(5)、渡辺 雅彦(2)、伊藤 誠二(6)、小林 拓也(1)
1. 関西医科大学、2. 北海道大学大学院医学研究院、3. 富山大学医学部学術研究部医学系、4. 新潟大学脳研究所、5. 藤田医科大学総合医科学研究所、6. 大阪医科大学
*Tayo Katano(1), Kotaro Konno(2), Keizo Takao(3), Manabu Abe(4), Kenji Sakimura(4), Tsuyoshi Miyakawa(5), Masahiko Watanabe(2), Seiji Ito(6), Takuya Kobayashi(1)
1. Kansai medical university, Osaka, Japan, 2. Grad Sch Med, Univ of Hokkaido, Hokkaido, Japan, 3. Grad Sch Innovative Life Sci, Univ of Toyama, Toyama, Japain, 4. Brain Res Insti, Niigata University, 5. Div Sys Med Sci, Fujita Health University, Aichi, Japan, 6. Osaka Medical College, Osaka, Japan
Keyword: BEGAIN, postsynaptic density, hippocampus, memory formation
In our previous study, we identified brain enriched guanylate kinase associated protein (BEGAIN), which functionally interacts with GluN2B-NMDA receptors in the spinal dorsal horn after nerve injury. Also, we clarified that BEGAIN was highly concentrated in the postsynaptic density (PSD) fraction not only the spinal dorsal horn but also hippocampus by western blotting. However, nothing is known about the role of BEGAIN in the hippocampus, such as memory formation.To clarify the contribution of the BEGAIN protein to memory formation, the Barnes circular maze and fear conditioning test were performed on BEGAIN-KO mice. In the learning process of the Barnes Maze test, there was no significant difference in the number of errors to target hole between wild-type and BEGAIN-KO mice. On the other hand, the time spent around the target hole for 24 hours after learning was reduced in BEGAIN-KO mice. In the fear conditioning, there was no significant difference in the physiological pain responses to electric shock (distance traveled), but the freezing rate of BEGAIN-KO mice was lower than that of wild-type mice. However, no difference was observed by the genotype after 24 hours in freezing of contextual and cues fear conditioning trials, whereas the freezing after 4 weeks was significantly shorter in BEGAIN-KO mice. Using the BEGAIN Cre-driver mice, we confirmed the expression of BEGAIN protein in the brain and showed that BEGAIN was highly expressed in the hippocampus. In addition, immunoelectron microscopy demonstrated that gold particles for BEGAIN were detected in the PSD at asymmetric synapses, but not symmetric synapses in the hippocampus. Our findings indicate that BEGAIN is involved in hippocampus-dependent memory formation at the excitatory postsynaptic site via functional interaction to postsynaptic proteins such as NMDA receptors. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-206
自伝的エピソード記憶の現象的特性に関する神経表象: fMRI研究
Multivariate neural representations of phenomenological qualities of autobiographical episodic memory: An fMRI study
*橋本 龍一郎(1,2)、青木 隆太(1,2)、板橋 貴史(2)
1. 東京都立大学、2. 昭和大学
*Ryuichiro Hashimoto(1,2), Ryuta Aoki(1,2), Takashi Itahashi(2)
1. Tokyo Metropolitan University, 2. Showa University
Keyword: AUTOBIOGRAPHICAL MEMORY, DEFAULT MODE NETWORK, COUNTERFACTUAL SIMULATION
The autobiographical memory (AM) system serves not only as a passive storage of one’s past life events but also as a basis for constructing cognitive schema of self, which is thought to develop through elaborate recollective processes such as counterfactual thinking. Memories for events that play particularly important roles for self are called “self-defining memories”, which are characterized by particular phenomenological qualities including emotion and vividness. Previous neuroimaging studies identified a set of brain structures supporting AM and some of them further attempted subdivision of the AM system based on psychological distinctions such as episodic versus semantic. However, it remains unknown how the AM system represents phenomenological qualities of past episodes. It also remains unexplored how neural representations for phenomenological qualities of episodes are modulated depending on the mode of recollection. In order to address these questions, we used an fMRI and measured brain activation from 28 young adults (13 females) while recollecting past episodes. On the first visit, each individual described 36 episodes and, as to each episode, evaluated 15 phenomenological qualities measures including emotion and event centrality. On the second visit, the participant underwent an fMRI session in which he or she was asked to recollect episodes as accurately as possible (REC condition) or by simulating counterfactually (SIM condition). fMRI data were acquired on a 3-T MRI scanner (Siemens, Germany). We used SPM12 for preprocessing and statistical analyses. The Decoding Toolbox was also used to perform multivariate pattern analysis (MVPA) to examine correlation between behavioral and neuronal dimensions. We first directly compared brain activations during the two modes of recollection. While the bilateral retrosplenial cortex showed significantly larger activation for the REC condition, an extensive brain network including frontoparietal and cerebellar regions showed larger activation for the SIM condition (P < 0.05, cluster-level corrected). In the following representation similarity analysis using the phenomenological measures of episodes, no significant voxel cluster was observed for the REC condition. In contrast, significant clusters were identified in regions including medial and lateral parietal cortex in the SIM condition. These results indicate that neural representations of phenomenological qualities of AM are manifested in the medial and lateral parietal cortex through constructive simulation. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-207
海馬と嗅内皮質における領域・細胞層・細胞種特異的なスパイク伝達効率の短期可塑性
Subregion-, cell layer-, and cell type-specific short-term plasticity of spike transmission probability in the hippocampus-entorhinal cortex circuit
*岩瀬 元貞(1)、水関 健司(1)
1. 大阪市立大学 大学院医学研究科 神経生理学
*Motosada Iwase(1), Kenji Mizuseki(1)
1. Department of Physiology, Osaka City University Graduate School of Medicine
Keyword: hippocampus, entorhinal cortex, synapse, spike transmission probability
Synaptic strength between two neurons is modified depending on the pre- and post-synaptic spike history occurring in timescales from a millisecond to thousands of milliseconds. This phenomenon, called short-term plasticity (STP) of synapses, is a fundamental property defying how information is transmitted in neural circuits. STP is classified as short-term depression (STD) and short-term facilitation (STF) (Regehr, 2012). STD and STF operate as low-pass and high-pass filters, respectively, and their appropriate combination is a basis for neuronal computation and causes synchronized firing patterns of neuron populations (Fortune and Rose, 2000; Loebel and Tsodyks 2002). STP has been intensively characterized in vitro by measuring subthreshold membrane potentials of post-synaptic neurons. Yet, STP is not well investigated in behaving animals due to the technical difficulty of recording post-synaptic membrane potentials in vivo (Tsodyks and Markram, 1997), thus limiting our understanding of STP function in the brain under operation. To address this question, we estimated STP properties of synapses using spike transmission probabilities as a proxy of synaptic weights with the datasets recorded from the hippocampus and entorhinal cortex (Mizuseki et al., 2014), which are brain regions essential for spatial navigation and episodic memory. To statistically evaluate the spike transmission provability, we confine our analysis to synapses from principal neurons to interneurons. We found that spike transmission potentiation and depression depend on the subregions and layers in the hippocampal-entorhinal circuit. Notably, consistent with the previous report (English et al., 2017), we found that short-term plasticity of spike transmission probability did not necessarily depend on the cell types of post-synaptic neurons. In addition, we examined whether short-term plasticity of spike transmission probability is consistent regardless of brain state (awake, REM sleep and slow-wave sleep). Our findings help understand the property of short-term synaptic plasticity in behaving animals and constrain the theory of computation in the hippocampal-entorhinal circuit. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-208
The Effects of Hibernation-like State on Memory
*Yu-Ju Lin(1), Ai Takahashi(1), Bruno Humbel(1), Takeshi Sakurai(2), Kazumasa Zen Tanaka(1)
1. Okinawa Institute of Science and Technology Graduate University (OIST), 1919-1 Tancha, Onna-son, Kunigami-gun, Okinawa, Japan 904-0495, 2. International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, Japan 305-8575
Keyword: Memory, Hibernation, Engram
Hibernation is a physiological condition characterized by low body temperature and metabolism to conserve energy in harsh environments. It has been shown that in wild-hibernating animals, the hippocampus undergoes significant rewiring, including changes in dendritic branching and spine densities (Popov et al., 1992). Interestingly, behavioral studies showed cognitive enhancements despite the drastic changes in neuronal morphology during hibernation (Weltzin et al., 2006) and memories obtained before hibernation retained after arousal from hibernation (Clemens et al., 2009). However, the neural mechanism that supports the memory during hibernation remains unclear. To address this fundamental problem, we used newly-developed transgenic mice. Discovering the thermoregulating QRFP-producing neurons (Q neurons) in the hypothalamus, Takahashi and colleagues established a Q-neuron-induced hypothermia and hypometabolism (QIH) state by chemogenetically activating the Q neurons (Takahashi et al., 2020). The state captures features that simulate natural hibernation, such as decreased heart rate, respiratory rate, locomotor activity, and food intake. This transgenic mouse line is an excellent tool to investigate the effects of the hibernation-like state on memories, cognitive abilities, and morphology in a well-controlled experimental setting. Using the Qrfp-iCre/c-Fos-tTA double transgenic mice, we first test the retention of various memories acquired before QIH induction, including contextual fear, tone-dependent fear, spatial, and social memories. Our preliminary data suggested that contextual fear memory encoded before the QIH was retained after mice fully recovered from the QIH state. Furthermore, we label the c-Fos positive memory engram during encoding to determine the functional contribution of the overlapping neuronal ensembles during memory retrieval after QIH. Additionally, we will examine the morphological changes in the hippocampus pre, during, and post QIH with electron microscopy. Our findings will provide insight into how memories can withstand global synaptic changes that may compromise the accurate neuronal network to support individual memories. Further, our results will help build the scientific basis for researching the potential medical applications in artificially induced hibernation. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-209
Frugal learning: Reducing the energetic costs of learning by restricting plasticity
*Silviu Daniel Ungureanu(1), Mark C. W. van Rossum(1,2)
1. School of Psychology, University of Nottingham, Nottingham, United Kingdom, 2. School of Mathematical Sciences, University of Nottingham, Nottingham, United Kingdom
Keyword: Energy, Synaptic plasticity, Learning, Artificial neural networks
In biological networks, synaptic updates during learning are sparse, but the reason for this is unclear. In contrast, artificial neural networks are nowadays commonly trained with backpropagation, updating all synapses in the network on every trial. It is known, however, that the brain consumes significant amounts of energy, and that learning processes like synaptic plasticity are metabolically expensive. We hypothesize that the sparse plasticity in biology helps to save metabolic energy.
We define a parsimonious model of energy consumption, representing energy-intensive processes such as de novo protein synthesis. We subsequently show that sparse, biologically-plausible learning algorithms can save a significant amount of energy while still reaching high performance. We explore two possible strategies.
The first is to randomly select at each training step a subset of neurons which can undergo plasticity, while the weights of the other neurons remain unmodified. In large networks, this saves over 50% of training energy compared to traditional training. In the second strategy, only a small number of neurons are plastic, while the rest have their initial weights frozen throughout training. This also significantly improves energy efficiency, with larger, over-parameterized networks saving between 60% and 75% in metabolic costs. Notably, a smaller fraction of plastic neurons leads to greater energy savings, but the presence of a small set of plastic neurons is crucial, as a network with a completely frozen hidden layer consumes more energy than an unmodified network. Moreover, such networks perform better than an equivalent standard network with the same number of plastic hidden layer units, achieving a higher accuracy.
Under both strategies, we observe the highest reduction in energy when the networks are much larger than the task requires, which is arguably the case for most biological learning. These findings illustrate that the restricted synaptic plasticity reported in the experimental literature does not deteriorate learning performance, and can be interpreted as a strategy to save the metabolic energy needed for plasticity. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-210
A Cyclic Ketogenic Diet Enhances Paired Associates Learning in a Rodent Model
*Tara Cooper(1), John Thompson(1), Cory Watson(1), Michelle McGrath(1), Abbi Hernandez(2), Sara Burke(1)
1. Dept Neuroscience, Univ of Florida, Gainesville, United States, 2. Univ of Alabama Birmingham, Birmingham, United States
Keyword: Paired Associates Learning, Metabolism, Aging, Ketogenic Diet
Age-related cognitive dysfunction, exacerbated by pathologies comorbid with aging such as Alzheimer’s Disease, greatly impacts quality of life and ability of older adults to live independently. Recent studies suggest that a ketogenic diet might mitigate biochemical alterations affiliated with advanced aging and improve performance on learning and memory tasks in a rat model of cognitive aging. Long-term carbohydrate restriction, however, can be challenging or unrealistic for many adults that show low compliance with diet-based interventions. This is particularly evident in persons living with Alzheimer’s who show increased cravings for high-carbohydrate foods. Furthermore, the magnitude of cognitive decline has been negatively correlated with treatment adherence. Thus, the current project tested the extent to which a novel cyclic ketogenic diet, which consisted of weekly changes between a high-fat low-carbohydrate ketogenic diet and a control diet, could match the efficacy of a standard long-term ketogenic diet. The potential clinical utility of enhancing metabolic flexibility induced by ketogenic cycling for mitigating age-related memory deficits was assessed with the Paired Associates Learning (PAL) task. The rodent PAL task is used to assess age-related cognitive decline by testing learning of object-location associations. Given previous data indicating improved performance in animals on a ketogenic diet on a hippocampal-dependent Working Memory Biconditional Association Task, we hypothesize that aged animals on a weekly cycling diet will show improved PAL task performance compared to a control diet group. Preliminary data of both young and aged animals shows that performance on the PAL task improved in the cyclic ketogenic diet group compared to both long-term keto and control diet groups. Furthermore, there does not seem to be variation in performance on control compared to ketogenic diet weeks within the cycling group, suggesting that metabolic flexibility rather than a state of ketosis may be a driving factor in mitigating age-related cognitive decline. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-211
メマンチンによるコンドロイチン硫酸の増加と海馬神経新生の促進
Improvement of cognitive function via increased synthesis of chondroitin sulfate by memantine
*山田 純(1)、前田 祥一朗(1)、飯沼 今日子(1)、神野 尚三(1)
1. 九州大学医学研究院
*Jun Yamada(1), Shoichiro Maeda(1), Kyoko M Iinuma(1), Shozo Jinno(1)
1. Grad Sch Med Sci, Kyushu Univ, Fukuoka, Japan
Keyword: Neurogenesis, Hippocampus, Memantine
Chondroitin sulfate proteoglycan (CSPG) constitutes a neurogenic niche in the adult hippocampus. Previous studies have indicated that reduction of newborn granule cells in the hippocampus may underlie the aging-related cognitive impairment. Because have recently reported that CSPG may promote the differentiation and maturation of NPCs in the adult mouse hippocampus, here we aimed to understand the potential involvement of CSPG in the pharmacological action of an approved anti-dementia drug memantine (MEM), an open-channel blocker of the NMDA receptor. To this end, middle-aged mice were treated with intraperitoneal injection of MEM (30 mg/kg) for three weeks. The expression of CSPG and densities of newborn granule cells in the hippocampus were increased by MEM. The expression levels of genes related to the biosynthesis and degradation of CSPG in the hippocampus were increased and decreased by MEM, respectively. The content of CSPGs in the hippocampus measured by high performance liquid chromatography were increased by MEM. A series of behavioral tests, such as the open field test, elevated plus maze test, Y-maze test, and fear conditioning test, were conducted to assess the effects of MEM. Anxiety-related behavior was reduced by MEM, and short- and long-term memory performance were improved by MEM. The same set of behavioral tests was used to evaluate the effects of pharmacological degradation of CSPG by chondtroitinase ABC. Depletion of CSPG in the hippocampus reduced the new granule cell production, and impaired the improvement of cognitive function by MEM. In summary, MEM may be involved in regulation of genes related to CSPG biosynthesis and degradation, which may underlie the improvement of cognitive function via promotion of adult hippocampal neurogenesis by MEM. These results also imply that CSPG may be a novel target for the anti-dementia drug. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-212
恐怖記憶の形成および消去に伴うミクログリアにおける遺伝子発現変化
Gene expression profiling of microglia after contextual fear conditioning
*兪 志前(1)、坂井 舞(1)、小野 千晶(1)、富田 博秋(1)
1. 東北大学医学系研究科
*Zhiqian Yu(1), Mai Sakai(1), Chiaki Ono(1), Hiroaki Tomita(1)
1. Grad Sch Med, Tohoku Univ, Sendai, Japan
Keyword: Microglia, Fear memory, Synapse
In the central nervous system (CNS), microglia based on innate immune functions enable detecting signals ranging from neuronal activity changes to damage. This study characterized the transcription profiling of microglia in the PTSD mice model. Furthermore, the mice transcription profiling was compared with the GEO database of PTSD patients to investigate potential genetic biomarkers associated with improved PTSD symptoms by effective treatment. As a result, most significantly induced synapse-related genes, while the reduced immune-related genes were changed in the mice microglia due to fear memory consolidation. After fear memory extinction, the increased synapse-related genes were recovered but not those of immunological genes, strongly suggesting a junction between microglia with neuron and immune dysfunction response to the contextual fear conditioning. Furthermore, we identified that expression of microglial GAGBA receptor and Synapsin, the key regulators of neurotransmitter release, was significantly changed according to contextual fear conditioning. In addition, compared with the transcription profiling in peripheral blood from PTSD patients being treated, commonly altered circadian rhythms-related genes have been confirmed after fear memory extinction and improved PTSD symptoms. Taken together, our findings identify the transcripts profiling in mice microglia contribute to neuron interaction, which may participate in microglia-neuron communication mediating contextual fear conditioning. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-213
NMDAによるCaMKII-RhoA-Rho-kinase経路の活性化が忌避学習を制御する
NMDA-induced activation of the CaMKII-RhoA-Rho-kinase pathway regulates aversive learning
*船橋 靖広(1)、Ahammad Rijwan Uddin (2)、張 心健(3)、Emran Hossen (1)、Faruk Md. Omar(2)、許 伊凡(1)、呉 敏華(4)、王 緩緩 (2)、黒田 啓介(2)、坪井 大輔(1)、西岡 朋生(1)、天野 睦紀(2)、崎村 建司(5)、内野 茂夫(6)、山田 清文(4)、永井 拓(3)、貝淵 弘三(1,2)
1. 藤田医科大学 総合医科学研究所、2. 名古屋大学大学院医学系研究科 神経情報薬理学、3. 藤田医科大学 精神・神経病態解明センター 神経行動薬理学研究部門、4. 名古屋大学大学院医学系研究科 医療薬学、5. 新潟大学 脳研究所 モデル動物開発分野、6. 帝京大学 理工学部 バイオサイエンス学科
*Yasuhiro Funahashi(1), Rijwan Uddin Ahammad(2), Xinjian Zhang(3), Hossen Emran(1), Md. Omar Faruk(2), Yifan Xu (1), Minhua Wu(4), Huanhuan Wang(2), Keisuke Kuroda(2), Daisuke Tsuboi (1), Tomoki Nishioka (1), Mutsuki Amano(2), Kenji Sakimura(5), Shigeo Uchino(6), Kiyofumi Yamada(4), Taku Nagai(3), Kozo Kaibuchi (1,2)
1. Institute for Comprehensive Medical Science, Fujita Health University, 2. Department of Cell Pharmacology, Nagoya University Graduate School of Medicine, 3. Division of Behavioral Neuropharmacology, International Center for Brain Science (ICBS), Fujita Health University, 4. Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine, 5. Department of Animal Model Development, Brain Research Institute, Niigata University, 6. Department of Biosciences, School of Science and Engineering, Teikyo University
Keyword: Glutamate, Phosphorylation, Signal transduction, learning
Glutamate induces Ca2+ influx in neurons through NMDA receptor (NMDAR) and consequently activates protein kinases, including CaMKII, which plays critical roles in postsynaptic functions and learning. However, how CaMKII regulates learning remains largely unknown. Here, we show that NMDA-induced activation of the CaMKII-RhoA-Rho-kinase pathway regulates aversive learning through Shank3 phosphorylation. We performed phosphoproteomics to identify CaMKII substrates and identified more than 100 phosphoproteins that respond to NMDA stimulation in the mouse striatum/nucleus accumbens (NAc). We found that CaMKII phosphorylated ArhGEF2 (RhoGEF) and stimulated its RhoGEF activity downstream of NMDAR. Aversive stimuli (electric foot shock) induced CaMKII-mediated ArhGEF2 phosphorylation and Rho-kinase/ROCK activation in the NAc. Inhibition of Rho-kinase in dopamine D2 receptor (D2R)-expressing medium spiny neurons (MSNs) in the NAc attenuated aversive learning. We also identified Shank3, an adapter protein of AMPA and NMDA receptors in postsynaptic density, as a novel Rho-kinase substrate. NMDA-induced Rho-kinase activation increased phosphorylation of Shank3 and regulates the interaction of Shank3 with NMDA and AMPA receptors. Manipulation of Shank3 in D2R-MSNs regulated dendritic spine morphology and aversive learning in a phosphorylation-dependent manner. These results demonstrated that NMDA-induced phosphorylation of Shank3 via the CaMKII-Rho-kinase pathway regulates aversive learning. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-214
ガストリン放出ペプチドはドーパミンシグナリングを介しストレスによる恐怖学習の亢進を制御する
The gastrin-releasing peptide regulates stress-enhanced fear and dopamine signaling
*森下 良一(1,8)、Ileana Fuentes(1)、John Favate(1)、Sofia Gonzalez(1)、Jennifer Mejaes(3)、Ko Zushida(1)、Akinori Nishi(1)、Charles Hevi(1)、Noriko Goldsmith(2)、Steve Buyske(4)、Stephanie E. Sillivan(5)、Courtney A. Miller(5)、Eric R. Kandel(6)、Shusaku Uchida(7)、David Barker(3)、Premal Shah(1)、Gleb P. Shumyatsky(1)
8. 名古屋市立大学 大学院医学研究科
*Yoshikazu Morishita(1,8), Ileana Fuentes(1), John Favate(1), Sofia Gonzalez(1), Jennifer Mejaes(3), Ko Zushida(1), Akinori Nishi(1), Charles Hevi(1), Noriko Goldsmith(2), Steve Buyske(4), Stephanie E. Sillivan(5), Courtney A. Miller(5), Eric R. Kandel(6), Shusaku Uchida(7), David Barker(3), Premal Shah(1), Gleb P. Shumyatsky(1)
1. Dept. of Genetics, Rutgers University, Piscataway, NJ, USA, 2. Keck Center, Rutgers University, Piscataway, NJ, USA, 3. Dept. of Psychology, Rutgers University, Piscataway, NJ, USA, 4. Dept. of Statistics, Rutgers University, Piscataway, NJ, USA, 5. Dept. of Molecular Medicine, The Scripps Research Institute, Jupiter, Florida, USA, 6. Howard Hughes Medical Institute, Columbia University, New York, NY, USA, 7. Grad Sch Med, Kyoto Univ, Kyoto, Japan, 8. Grad Sch Med, Nagoya City Univ, Nagoya, Japan
Keyword: memory, gastrin-releasing peptide, dopamine
Fear extinction is an adaptive behavioral process critical for organisms survival, but the deficiency in extinction may lead to PTSD. While the amygdala and its neural circuits are critical for fear extinction, the molecular identity and organizational logic of cell types that lie at the core of these circuits remain unclear. One of the approaches towards this goal is to dissect at the molecular level region-restricted neural networks. Earlier, we identified the gastrin-releasing peptide (Grp) gene, as enriched in the neural circuitry of learned fear (Shumyatsky et al., Cell 2002). In the current study, we found that mice deficient for gastrin-releasing peptide gene (Grp-/-) exhibit enhanced neuronal activity in the basolateral amygdala (BLA) and stronger fear conditioning, as well as deficient extinction in stress-enhanced fear learning (SEFL). rAAV2-retro-based tracing combined with visualization of the GFP knocked in the Grp gene showed that BLA receives GRPergic or conditioned stimulus projections from the indirect auditory thalamus-to-auditory cortex pathway, ventral hippocampus, and ventral tegmental area. Interestingly, it appears that dopamine responses induced by presentation of tone or shock are larger in the Grp-/- than in the WT mice resulting in stronger fear learning. On the other hand, transcription of dopamine-related genes was decreased in BLA of Grp-/- mice following SEFL extinction recall, suggesting a compensatory mechanism against an enhanced dopamine release. Taken together, it is possible that the GRP is critical for regulating the dopamine-releasing mechanism that dedicates to fear learning and extinction learning. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-215
行動刺激依存的に活動するアストロサイト集団への遺伝学的アプローチ
A genetic approach for tagging behaviorally-activated astrocyte ensembles.
*出羽 健一(1)、Bolati Wulaer(1)、笠井 淳司(2)、長井 淳(1)
1. 理化学研究所 脳神経科学研究センター グリア-神経回路動態研究チーム、2. 大阪大学大学院薬学研究科 神経薬理学分野
*Ken-ichi Dewa(1), Wulaer Bolati(1), Astushi Kasai(2), Jun Nagai(1)
1. Laboratory for Glia-Neuron Circuit Dynamics, RIKEN Center for Brain Science, Wako, Japan, 2. Laboratory of Molecular Neuropharmacology, Graduate School of Pharmaceutical Sciences, Osaka University
Keyword: Astrocyte, Behavior
Astrocytes encompass neurons and vasculature for monitoring and/or controlling neuronal activity and synaptic transmission. However, their signaling dynamics, brain region-specific functions and behavioral consequences are incompletely understood. Recently, RNA-sequencing revealed that astrocytes differ by distinct brain region with gene expression profiles and mount distinct molecular responses to various brain state transitions (i.e. molecular diversity). In addition, behaviorally-relevant stimuli activate a fraction of astrocytes across brain areas. Here we tackle the question of where and how astrocyte populations respond to particular behaviorally-relevant stimuli or brain state transitions. We aim to capture and manipulate Behaviorally-activated Astrocyte Ensembles (BAE [bei]) to reveal their consequential roles in circuits and behavior. To this end, we constructed a new AAV-based genetic tool for brain-wide, astrocyte selective activity tagging. The AAV PHP.eB serotype can breach the BBB following injection into the bloodstream and reach all regions of the brain. Combining this tool with whole-brain mapping by block-face serial microscopy tomography (FAST), we were able to detect activated astrocytes in the whole brain. We performed pharmaco-genetic stimulation of astrocytes in a local neural circuit with this tool, and found that the stimulation remotely activate astrocyte in other brain regions. We provide a platform to detect and map out the distribution of astrocytes that were activated by behavior and pharmaco-genetic stimulation. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-216
連合記憶課題の学習過程における海馬CA1と聴覚皮質ニューロン活動のダイナミクス
Dynamics of neural activities in hippcampal CA1 and auditory cortex during learning process of an associative memory task.
*高宮 渉吾(1)、櫻井 芳雄(1)
1. 同志社大学大学院脳科学研究科
*Shogo Takamiya(1), Yoshio Sakurai(1)
1. Graduate School of Brain Science, Doshisha University
Keyword: hippocampus, auditory cortex, learning and memory, neural recordings
The hippocampus and neocortex are crucial for forming association between environment stimuli. However, it is unclear how neural avtivities of hippocampal and neocortical neurons dynamically change during the learning process. To adress this question, we developed an associative memory task for rats with auditory stimuli. In this task, the rats were required to associate tone pitches (high or low) and ports (right and left) to obtain a reward. We recorded the firing activity of neurons in rats hippocampal CA1 (HPC) and primary auditory cortex (AC) during the learning process of the task. As a result, many HPC neurons and some AC neurons modulated their firing rates in response to choice-direction regardless of tone piches. We referred to these cells as “Choice-direction cells”. On the other hand, many AC neurons modulated their firing rates in response to tone pitches regardless of choice-direction, although few HPC neurons did that. We referred to these cells as “Tone selective cells”. Some HPC and AC neurons also modulated their firing rates when the rats recieved a reward after choosing either the left or right port. We referred to these cells as “Reward-direction cells”. The proportions of tone selective cells in AC significantly increase in late stage of learning stages, although the proportions of choice-direction cells in HPC and AC were not significantly different among learning process. Futhermore, the proportion of reward-direction cells in HPC increased in middle-stage of learning but decreased after the completion of learning. On the other hand, The proportions of reward-direction cells in AC significantly increase in late stage of learning stages. Our results show that HPC and AC neurons play a different role in acquisition of association between auditory cue and direction choice. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-217
幼若および成体マウスの新規物体認識行動と嗅皮質神経回路のin vitro膜電位イメージング
Novel object recognition behavior of juvenile and adult mice and the voltage-sensitive dye imaging of its rhinal cortical circuits in vitro
*井出 悠也(1)、井上 翼(1)、斎藤 雄輝(1)、岩岡 みほり(1)、冨永 貴志(2)、梶原 利一(1)
1. 明治大学、2. 徳島文理大学
*Yuya Ide(1), Tsubasa Inoue(1), Yuki Saito(1), Mihori Iwaoka(1), Takashi Tominaga(2), Riichi Kajiwara(1)
1. Meiji University, 2. Tokushima Bunri University
Keyword: Novel object recognition, voltage-sensitive dye imaging, perirhinal cortex
The rhinal cortices, such as the perirhinal cortex (PC) and the entorhinal cortex (EC), are located within the bidirectional pathway between the neocortex and the hippocampus (HiP). This anatomical structure is essential for the hippocampus to communicate and interact with the neocortex, but it also has the property that each brain region works independently according to the behavioral demands. For example, in the Novel Object Recognition (NOR) test for mice, it has been shown that immediate early response genes are expressed in both PC and HiP under different behavioral conditions. Since these brain regions show significant morphological and synaptic development in the early postnatal period, this study addressed the following questions. Is there a change in object recognition memory behavior during development? In addition, are there any changes in the neural activity pattern of the PC-EC-Hip circuit?
We classified male C57BL/6J mice into three groups: juvenile (3~4 weeks old), young (5~7 weeks old), and adult (8 weeks old or later), and examined whether there were differences in novel object recognition behavior in each group. The experiment was conducted in three phases: a habituation session (S0), a training session (T1), and a test session (T2) using a square chamber of gray PVC board measuring 40 × 40 × 40 cm. In T1, which was conducted 24 hours after S0, two identical objects were placed in a chamber at a distance of 15 cm from each other, 12.5 cm from the sides, and allowed to explore for 10 minutes. Twenty-four hours later, one of the objects was replaced with a new object, and the mouse was allowed to explore again for 10 minutes (T2). The mean novel object discrimination index of each group was tested by one-way ANOVA, and the result showed that the search time for novel objects was predominantly larger in adult mice than in familiar objects, while juvenile mice did not show any preference for novel objects.
To examine whether these developmental differences in behavior are also observed in the pattern of neural excitatory propagation between PC-EC-HiP, we applied the VSD imaging method to mouse brain slices after conducting the behavioral experiment. In the experiment, we stimulated the superficial layers of the PC under the perfusion of 0.5 µM of gabazine, a GABA-A receptor antagonist. In the adult group, no neural activities propagated to the EC under the condition. On the other side, the evoked activity in the PC often propagated to the EC in the juvenile group. We analyzed the ratio of time-integrated values of optical signals before and after gabazine perfusion and found a significant difference between the juvenile and mature groups. The differences in the NOR test observed during the developmental period may reflect differences in the inhibitory system of the rhinal cortices. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-218
Dynamic and pathway-specific signaling in the dorsomedial striatum and dopamine neurons during behavioral adaptation
*Alain Rios(1), Satoshi Nonomura(2), Yutaka Sakai(4), Shigeki Kato(3), Kazuto Kobayashi(3), Masahiko Takada(2), Yoshikazu Isomura(1), Minoru Kimura(4)
1. Department of Physiology and Cell Biology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 2. Systems Neuroscience Section, Primate Research Institute, Kyoto University, 3. Department of Molecular Genetics, Institute of Biomedical Science, Fukushima Medical University, 4. Brain Science Institute, Tamagawa University
Keyword: Basal Ganglia, Behavioral adaptation, Dorsomedial Striatum, Dopamine
In our previous study, we demonstrated that direct pathway spiny projection neurons (dSPNs) in the rat dorsomedial striatum (DMS) encode chosen action-associated reward, while indirect spiny projection neurons (iSPNs) encode no-reward outcomes. We have further shown that optogenetic activation of dSPNs and iSPNs biases toward repeating or switching actions, respectively, indicating monitoring and updating of action selection for goal directed behavior (Nonomura, 2018). However, it remains unclear how the pathway-specific signaling is modified through behavioral adaptation to changes of environment. We addressed this issue by investigating dynamic neuron properties in the DMS and the substantia nigra pars compacta (SNc). As previously reported, Tac1-Cre (n=6) and Drd2-Cre rats (n=6) pushed or pulled a lever with the right forelimb for water reward. Probabilities of reward after action selection were fixed (80 vs 20 or 70 vs10) for 30-70 trials and reversed without external cue. Activities of optogenetically tagged dSPNs (n=25) and iSPNs (n=22) were recorded from the left DMS using silicon probe. The DMS-projecting dopamine neurons (n=19) were identified in the medial SNc by antidromic activation in TH-Cre rats (n=7). After reversal of action-outcome association, the rats changed selection from high-value action (HVA) to the currently higher-value one in a trial-and-error manner within 10 to 30 trials. Then, they selected that action in most trials (>80%). In a small number of trials after reaching the stable HVA-selection stage, the rats tried low-value action (LVA). The rats switched selection if the action resulted in no-reward at a lower probability after HVA (switch prob. 0.36) than LVA selection (prob. 0.76), indicating stronger belief in HVA than LVA selection. All the dSPNs, iSPNs, and DMS-projecting dopamine neurons exhibited stronger activation in HVA than LVA selection. Reward-instructing tone after selection of HVA and LVA activated dSPNs and dopamine neurons but suppressed iSPNs, whereas no-reward tone suppressed SNc neurons but activated iSPNs. These neuron type-specific signals during the action and outcome periods occurred at short latency (<500ms). At longer latency (>500 ms) after no-reward tone, however, iSPNs showed robust, long-lasting activation after LVA but not after HVA selection. Thus, the dynamic and pathway-specific signaling in the DMS and dopamine input may represent basal ganglia mechanisms underlying behavioral adaptation. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-219
連合学習時の多領域にわたる神経集団活動
Neuronal population activity in multiple brain regions during associative learning
*平野 匡佑(1,2)、南 雅文(1)、野村 洋(1,2)
1. 北海道大学大学院薬学研究院、2. 名古屋市立大学大学院医学研究科
*Kyosuke Hirano(1,2), Masabumi Minami(1), Hiroshi Nomura(1,2)
1. Grad Sch Pharm, Hokkaido Univ, Hokkaido, Japan, 2. Grad Sch Med, Nagoya City Univ, Aichi, Japan
Keyword: memory, learning, in vivo Ca imaging
Information processing by cell assemblies within a brain region and by an interplay between multiple brain regions are essential for learning and memory. However, the study of the interplay between multiple brain regions and the study of the cell assemblies in individual brain regions have been conducted separately. Therefore, how the interplay of cell assemblies across multiple brain regions is related to learning and memory remains unclear. In this study, we examined how auditory-reward conditioning alters a relationship between cell assemblies in the medial geniculate body (MG) and lateral amygdala (LA). We injected adeno-associated virus (AAV) expressing a genetically encoded calcium indicator, GCaMP6f, into the MG and LA of C57/BL6J mice and implanted gradient refractive index (GRIN) lens above the two brain regions. Using in vivo calcium imaging, we recorded neuronal activity simultaneously from the MG and LA of the head-fixed behaving mice during the auditory-reward conditioning in which the animal was conditioned by delivering sucrose solution with a tone. Some MG cells and LA cells responded to tone or sucrose solution. As learning progressed, tone responsive cells decreased in the MG but not in the LA. In addition, we analyzed correlations between individual cells. In an early learning phase, inter-regional correlations between MG and LA cells were smaller than intra-region correlations. However, in a late learning phase, some inter-regional cell pairs showed high correlation. The highly-correlated, inter-regional cell pairs were only observed after associative learning but not after tone only presentation. These cell pairs show high correlation at tone-sucrose presentation but not at baseline. These results suggest that associative learning strengthens information flows between specific, inter-regional cell assemblies. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-220
安静時脳活動の動的特性とfMRIニューロフィードバック訓練への適応性との関連
A possible link between spontaneously explored brain dynamics at rest and driven brain state during fMRI-neurofeedback training
*髙村 真広(1,2)、中野 高志(3,4)、西村 春輝(5,6)、町澤 まろ(2)、市川 奈穂(2)、吉野 敦雄(2,7)、岡田 剛(7)、岡本 泰昌(2,7)、山脇 成人(2)、山田 真希子(5,6)、須原 哲也(5)、吉本 潤一郎(3,4)
1. 島根大学医学部、2. 広島大学脳・こころ・感性科学研究センター、3. 奈良先端科学技術大学院大学 先端科学技術研究科情報科学領域、4. 藤田医科大学医学部、5. 国立研究開発法人量子科学技術研究開発機構 量子生命科学研究所、6. 国立研究開発法人量子科学技術研究開発機構 脳機能イメージング研究部、7. 広島大学大学院医系科学研究科
*Masahiro Takamura(1,2), Takashi Nakano(3,4), Haruki Nishimura(5,6), Maro Machizawa(2), Naho Ichikawa(2), Atsuo Yoshino(2,7), Go Okada(7), Yasumasa Okamoto(2,7), Shigeto Yamawaki(2), Makiko Yamada(5,6), Tetsuya Suhara(5), Junichiro Yoshimoto(3,4)
1. Faculty of Medicine, Shimane University, Izumo, Japan, 2. Center for Brain, Mind and KANSEI Research Sciences, Hiroshima University, Hiroshima, Japan, 3. Division of Information Science, Graduate School of Science and Technology, Nara Institute of Science and Technology, Ikoma, Japan, 4. School of Medicine, Fujita Health University, Toyoake, 470-1192, Japan, 5. Institute of Quantum Life Science, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan, 6. Department of Functional Brain Imaging, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan, 7. Graduate School of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan
Keyword: NEUROFEEDBACK, RESTING-STATE fMRI, BRAIN DYNAMICS, ENERGY LANDSCAPE ANALYSIS
Neurofeedback (NF) is a technique for modulating brain function through feedback learning of brain activity, and its clinical application to various diseases has been attempted. It has been observed that there are individual differences in how well NF training can be performed. This “NF aptitude” variation has been a challenge for the therapeutic application of NF. In the previous study, we investigated the machine-learning prediction of NF aptitude from the resting-state functional brain connectivity pattern. As a result, we have identified a prediction model with high performance and generalizability to independent data. As a limitation, this model is based on the static functional connectivity calculated from the whole time-series data, and the dynamic aspect of the resting-state activity has not been examined. The present study reports results of energy landscape analysis on the relationship between NF training adaptivity and resting-state brain dynamics among the critical brain regions determined by our previous study. We analyzed resting-state fMRI data and NF adaptivity scores obtained from 25 healthy participants of our previous fMRI-NF study. First, from the preprocessed resting-state fMRI data, we extracted time-series signals in the following ROIs: the dorsolateral prefrontal cortex (DLPFC), posterior insula cortex (PIC), posterior cingulate cortex (PCC), precuneus (PreC), intraparietal sulcus (IPS), temporoparietal junction (TPJ), and superior parietal lobule (SPL). Next, the pairwise maximum entropy model was applied to the concatenated and binarized time-series data. This energy landscape analysis allows us to decompose the time-series signals of multiple brain regions into a number of stable states (basins) and analyze the transitions between these states. As a result of the modeling, 14 basins were obtained. Correlation analysis between the visiting frequency of each basin and NF adaptability revealed a significant positive correlation between the visiting frequency at Basin #6 and NF adaptability. Basin #6 corresponds to a brain state in which DLPFC, TPJ, and PIC are active and PCC, PreC, IPS, and SPL are inactive. This pattern is similar to the brain activity commonly observed during NF training, as revealed by a previous meta-analysis. This result suggests that the correspondence between brain activity patterns spontaneously explored at rest and those driven during NF training may be related to the adaptation to NF training. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-221
マウス海馬のコンドロイチン硫酸の発現と神経新生に対するリポ多糖 (LPS) とセサミンの作用に関する集学的解析
Alleviation of cognitive deficits via upregulation of chondroitin sulfate biosynthesis by lignan sesamin in the lipopolysaccharide-induced neuroinflammation model
*前田 祥一朗(1)、山田 純(1)、征矢 茉莉子(1)、飯沼 今日子(1)、神野 尚三(1)
1. 九州大学
*Shoichiro Maeda(1), Jun Yamada(1), Mariko Soya(1), Kyoko Iinuma(1), Shozo Jinno(1)
1. Kyushu University
Keyword: hippocampus, neurogenesis
Phytoestrogens act as partial estrogen agonists, and they are expected to have some beneficial effects for mental health. Although we have reported that phytoestrogen daidzein may promote adult hippocampal neurogenesis, the details remain unclear. In the present study, we aimed understand whether phytoestrogen lignan sesamin (SES) may affect chondroitin sulfate proteoglycan (CSPG) expression, because CSPG is involved in regulation of adult hippocampal neurogenesis. We first examined potential alterations in biosynthesis and degradation of CSPG by SES in lipopolysaccharide (LPS)-treated mice, an experimental model for neuroinflammation. Gene expressions of pro-inflammatory cytokine, interleukin-β, in the hippocampus of LPS- treated mice were decreased by SES. Expressions of genes related to CSPG biosynthesis and degradation were increased and decreased by SES in the hippocampus, respectively. The labeling of CSPG by Wisteria floribunda agglutinin (WFA) in the hippocampus was increased by SES. The densities of neural stem cells, late transit-amplifying cells, and newborn-granule cells in the hippocampus were increased by SES. Interestingly, SES-induced alterations in the gene expression, WFA labeling, and adult neurogenesis in LPS-treated mice were more evident in the dorsal hippocampus (center of cognition) than in the ventral hippocampus (center of emotion). Finally, we performed a series of behavioral tests to understand the effects of SES on cognitive function: open-field test, fear conditioning test, and prepulse inhibition test. Impairments of contextual fear memory and sensorimotor gating function in LPS-treated mice were recovered by SES administration. Our results indicate that SES can promote adult hippocampal neurogenesis through upregulation of CSPG, which may underlie alleviation of cognitive deficits induced by neuroinflammation. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-222
前帯状皮質のニューロンは投射先によって空間と報酬を別個に表現する
The projection neurons in anterior cingulate cortex projection separate spatial and reward information during spatial navigation
*李 耀龍(1)、水田 恒太郎(1)、林 康紀(1)、シュミット アレクサンダー(1,2)
1. 京都大学、2. マックスプランク研究所
*Yaolong Li(1), Kotaro Mizuta(1), Yasunori Hayashi(1), Alexander Schmidt(1,2)
1. Kyoto University, 2. Max Planck Institute for Dynamics and Self-Organization, Göttingen 37077, Germany
Keyword: SPATIAL MEMORY, ANTERIOR CINGULATE CORTEX, RETROGRADE TRACING, CALCIUM IMAGING
The anterior cingulate cortex (ACC) plays important roles in multiple functions such as decision making, spatial navigation. Neurons encoding different information such as context and space are found in ACC. ACC connects with multiple brain regions each involved in different functions. This raises a question how ACC separates different information and projects to other brain region. To address this question, we first labeled the projection neurons in ACC by injecting retrograde tracers into the dorsal-medial striatum (dmSTR) and the retrosplenial cortex (RSC) and found that distinct population of ACC neurons project to these two regions. ACC layer 2/3 neurons preferentially projected to dmSTR, whereas layer 5 neurons preferentially projected to RSC. The neurons projecting to both regions were few. To check whether these distinct projection neurons encode different information, we injected AAV2-retro-CaMKII-GCaMP6f into dmSTR or RSC to retrogradely labeled neurons in ACC. We then carried out two-photon calcium imaging under a virtual reality (VR) environment, consisting of a running track with a fixed reward delivery location. Mice could memorize the reward location. We found a subpopulation of ACC-dmSTR and ACC-RSC projection neurons were identified as place cells which fired when animal passed the specific location. In both ACC-dmSTR and ACC-RSC projection neurons, place cells were emerged gradually during learning and most ACC-RSC place cells were fired only in specific track. Interestingly, the place fields of ACC-dmSTR place cells were covered entire tracks, whereas the place fields of ACC-RSC place cells were concentrated around reward location. Then, we added one more reward location in the linear track and randomly delivered reward only at one reward location in each trial, we found that ACC-RSC place cells fired in both reward location and regardless of whether reward is delivered or not. It suggested that these neurons were not response to reward itself but memorized the reward location. Our results support the hypothesis that ACC separates different information and projects to other regions. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-223
Optogenetically induced sharp wave-ripples enhance sleep-dependent consolidation of episodic memory in rats
*Sypniewski Krzysztof(1)、Shoko Arai(1)、Pavlides Constantine(1)
*Krzysztof Andrzej Sypniewski(1), Arai Shoko(1), Constantine Pavlides(1)
1. Graduate School of Comprehensive Human Sciences, University of Tsukuba, Japan
Keyword: SHARP WAVE RIPPLES, HIPPOCAMPUS, MEMORY, OPTOGENETICS
Sharp wave ripples (SW-R) are distinct EEG complexes observed in the hippocampus during quiet wakefulness and slow wave sleep (SWS). Sleep-dependent memory consolidation is thought to be enhanced by SW-R activity: learning results in an increase of SW-R events during post-learning sleep, while suppressing SW-Rs leads to impaired long-term memory. Here, we present evidence that experimentally increasing the number of SW-R's during sleep enhances long-term memory in rats. In SWS, synchronous firing of a small population of CA3 pyramidal cells produces a large depolarization (i.e., sharp waves) which travels via Schaffer collaterals to the CA1 region initiating high frequency (100~250Hz) ‘ripple’ oscillations, superimposed at the peak of the sharp wave. We induced similar SW-R activity artificially in freely behaving rats via localized optogenetic stimulation of the CA3. The characteristics of the artificial SW-R (aSW-R) were comparable to natural ones. Importantly, the stimulation itself did not interrupt sleep and did not prevent natural SW-R activity from occurring. All rats underwent single-trial contextual fear conditioning using a mild protocol (2x, 1s foot-shock, 0.75mA, 2min inter-shock interval), to prevent potential ceiling effects. Following conditioning, animals were placed in an observation chamber for up to 5h for monitoring sleep states. Upon entering SWS, experimental group animals either received light stimulations (no more than once per 0.75s) to produce aSW-R (aSW-R[+] group) or served as non-stimulated controls (naive group). Long-term fear memory was tested 1-6d post conditioning. Freezing in both groups of animals was comparable (94.4±5.9% vs 91.7±4.1% for control and aSW-R [+], respectively) following conditioning. In the naive group, freezing was significantly lower (63.9 ±8.3; p < 0.01) than post-shock levels at the 24h retest and dropped further with each consecutive test day. In contrast, the aSW-R [+] group showed high freezing levels at 24h (86.3 ±5.0%) and at 2d (70.8 ±13.2%) with the drop in freezing reaching significance at d3 (50.8 ±12.9%; p< 0.01) of testing. Further, multiple t-test comparisons between groups showed that 24h after conditioning aSW-R[+] animals exhibited significantly higher (p<0.01) freezing levels, compared to non-stimulated controls. These findings provide direct evidence that SW-R density during post-learning sleep can enhance episodic memory consolidation. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-224
記憶固定化過程におけるシナプス伝達長期増強現象の脳内時空間分布の追跡
Spatio-temporal tracing of the distribution of potentiated synapses during memory consolidation
*小椋 星哉(1)、野場 真之介(1)、Shuo Li(2)、淺岡 希美(1)、林 康紀(1)
1. 京都大学大学院医学研究科
*Seiya Ogura(1), Shinnosuke Noba(1), Shuo Li(2), Nozomi Asaoka(1), Yasunori Hayashi(1)
1. Graduate School of Medicine, Kyoto university, Kyoto, Japan, 2. Zhongshan Medical Science University, Zhongshan, China
Keyword: memory consolidation, LTP, whole-cell recording, neural circuits
Episodic memory is initially formed in the hippocampus but stored for long-term in the rest of the brain. Therefore, for long-term storage, the memory needs to be transferred from the hippocampus to other brain regions in a process called memory consolidation. Recent studies have shed light on the roles of the anterior cingulate cortex (ACC) in the formation, maintenance, and retrieval of long-term memory. However, the neural pathways through which the hippocampal memory information is transferred to the ACC remain to be known. This study aimed to estimate a neural pathway of memory transition from the hippocampus to the ACC by identifying the spatial and temporal changes in neural activity and synaptic transmission. Fear memory was established in mice by inhibitory avoidance task. Then, the neural activity during memory retrieval with various intervals from the learning was assessed by the expression of c-fos, an immediately early gene. Whole-cell recording was also performed to examine a change in synaptic transmission after memory retrieval, testing where and when synaptic plasticity takes place. As a result, in addition to the hippocampus and ACC, the retrosplenial cortex (RSC) was identified as another region that shows upregulation of c-fos expression, indicating a delayed and transient neural activity several weeks after learning. Such transient upregulation of neural activity was followed by the activation of the ACC after more several weeks. The potentiation of the synaptic transmission was expressed in the hippocampal CA1 region prior to the RSC, but not expressed in the ACC, within 2 weeks after learning. These findings demonstrate the chronological shift of neural activity and synaptic potentiation in the order of the hippocampus, the RSC, and the ACC. Such spatio-temporal changes imply memory transition from the hippocampus to the ACC via RSC during memory consolidation, shifting the brain regions responsible for memory retrieval. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-225
Investigate the microbiota-gut-brain axis underlying dietary restriction-induced memory enhancement
*CHUN-CHIEH HUANG(1,2), PEI-YU WANG(1)
1. Grad Inst of Brain and Mind Sci, Natl Taiwan Univ, Coll of Med, Taipei, Taiwan, 2. Taiwan Int Grad prgm in Interdisciplinary Neurosci, Natl Taiwan Univ and Academia Sinica, Taipei, Taiwan
Keyword: Gut microbiome, Fecal transplantation, Learning and Memory, Multiomic
Dietary restriction (DR) is widely recognized as a beneficial food regimen to improve physiological conditions and alleviate age-related dysfunctions. It has shown consistent results in anti-inflammation, prolonging lifespan, and cognitive improvement with simple model organisms as well as humans. Recent studies demonstrated DR exerts several benefits through the microbiota-gut-brain axis. Our current research further established the necessity of the gut microbiota in DR-induced memory enhancement. We adopted two loss-of-function models to examine the role of the gut microbiota: antibiotics-treated mice and germ-free mice. Both approaches demonstrated that DR-induced memory enhancement can be abolished in the absence of gut microbiota. Moreover, the enhanced memory performance could be accomplished in mice under ad libitum (AL) condition receiving fecal microbiota transplantation from DR mice (FMT-DR). 16s rRNA sequencing identified common bacterial change in DR and FMT-DR. Furthermore, metabolomic experiments on feces and serum revealed a similar metabolic profile, providing a potential interface between microbial alteration and memory enhancement. These results further strengthen the role of the gut microbiota in regulating cognitive function and suggest microbial metabolites as a potential mediator of the microbiota-gut-brain axis underlying DR. Our study would provide a comprehensive understanding of the mechanism underlying DR-induced memory enhancement. The ultimate goal is to identify a suitable intervention to improve memory function as well as mitigate disease-related memory deficit. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-226
Memory Traces in Dissociated Cultures of Neurons
*Zhang Zhuo(1)、Yaron Amit(2)、Eisuke Suwa(1)、Shiramatsu Tomoyo (1)、Takahashi Hirokazu(1)
*Zhuo Zhang(1), Amit Yaron(2), Suwa Eisuke(1), Tomoyo Isoguchi Shiramatsu(1), Hirokazu Takahashi(1)
1. Graduate School of Information Science and Technology, The University of Tokyo, Tokyo, Japan, 2. International Research Center for Neurointelligence (WPI-IRCN), UTIAS, The University of Tokyo, Tokyo, Japan
Keyword: Memory traces, Dissociated cultures of neurons, Mismatch negativity, Memory replay
Memories will replay spontaneously during system integration, thereby forming memory traces (where one stimulus is associated with the second discontinuous and later stimulus). According to the "sensory memory" hypothesis, mismatch negativity (MMN) reflects the deviation properties of the nervous system between the properties of the neural "memory traces" established by the previous standard stimulation. Here, we used cultured neuronal networks on multielectrode arrays and an electro-stimulating approach to investigate the effect of memory replay on the formation of memory traces and deviant detection properties. The oddball conditions, omission conditions, and many standards control (MSC) conditions as electrical stimulation experimental paradigms. Our results showed that the response of neurons in the range of 50 ms before stimulation to 200 ms after stimulation to the deviant stimulation presented a significant difference from that of standard stimulation in the oddball experiment, that is, a stronger and more obvious second response to deviant stimulus appeared in the neuron network, while only an inconspicuous secondary response to the standard stimulus can be observed. In addition, under the omission scenario, the response of the neural network evoked by the standard equidistant stimulation is similar to that in the oddball standard condition. And when the stimulus was absent in a random way, the neuron network also produced a slight response. This result reflected the formation of memory traces under repeated standard stimulation, and in the absence of stimuli, the neural network responds "inertially" due to memory replay. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-227
脳状態変化に伴う神経信号・伝播特性変化
Basic properties of cortical wave of neuronal signals are governed by the state of the brain.
*道念 佑樹(1)、松井 広(1)
1. 東北大学大学院生命科学研究科
*Yuki Donen(1), Ko Matsui(1)
1. Grad Sch Life Science, Tohoku University, Sendai Japan
Keyword: Circadian rhythm, optogenetics, cortical signal transmission
World perception and representation are governed by the state of our mind. The same physical environment may evoke different responses to the same individual. Here, we investigated whether simple signal transmission of a delta pulse of neuronal excitation across the cortex can be influenced by the state of the brain. Using a transgenic rat that expresses photoactivatable channel protein, ChR2, in neurons, a short light pulse was delivered to the occipital lobe via an optical fiber to produce a concerted excitation of a population of neurons. The signal created would likely propagate from the occipital to the frontal lobe following an endogenous pathway of transmission of visual signals. Multiple electrodes were inserted along this pathway to measure the speed and amplitude of this signal transmission. Interestingly, in all of the regions recorded, a 24-hour cycle of fEPSP amplitude changes was observed. This cycle of circadian rhythm was stably repeated for multiple days. The magnitude of the maximum amplitude changes during the 24-hour differed depending on the location of the electrode, which suggests that the amplification gain of the delta pulse signal also has a circadian rhythm. As rats are nocturnal animals, they sleep less during the night and more during the day time. It is possible that the optogenetic stimuli given during sleep and awake states propagated differently. To test for this hypothesis, EEG and EMG were recorded to distinguish different sleep/awake states. In addition, we found a completely different circadian rhythm dependency of cortical signal transmission in aged (>1.5 years old) rats. Factors affecting properties of cortical signal waves were compared and cross analyzed between day/night, sleep/wake, and young/old age groups. Our results indicate that the same physical stimuli may be perceived and processed differently depending on the brain state. Simple fluctuations of basal concentration of transmitter such as adenosine and/or ionic/metabotropic factors could affect these cortical signal properties, which may have consequences even on higher cognitive brain functions | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-228
一過性低強度運動は青斑核-海馬背側部ドーパミン・ノルアドレナリン作動性神経経路を活性化する
Acute light intensity exercise activates dopaminergic and noradrenergic coeruleo-dorsal hippocampal pathway
*平賀 大一(1,2)、秦 俊陽(1,2)、下田 亮(1)、グレニエ フランソワ(1)、征矢 晋吾(3)、Johansen Joshua(4)、松井 崇(1,5)、岡本 正洋(1,5)、征矢 英昭(1,5)
1. 筑波大学運動生化学研究室、2. 日本学術振興会、3. 筑波大学国際統合睡眠医科学研究機構、4. 理科学研究所脳神経科学研究センター、5. 筑波大学体育系ヒューマン・ハイ・パフォーマンス先端研究センター
*Taichi Hiraga(1,2), Toshiaki Hata(1,2), Ryo Shimoda(1), Francois Grenier(1), Shingo Soya(3), Joshua P. Johansen(4), Takashi Matsui(1,5), Masahiro Okamoto(1,5), Hideaki Soya(1,5)
1. Exercise Biochem. & Neuroendocrinol., University of Tsukuba, Ibaraki, Japan, 2. Japan Society for the Promotion of Science, Tokyo, Japan, 3. International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Ibaraki, Japan, 4. RIKEN Center for Brain Science, Saitama, Japan, 5. Sport Neuroscience Division, Advanced Research Initiative for Human High Performance (ARIHHP), University of Tsukuba, Ibaraki, Japan
Keyword: light intensity exercise, locus coeruleus, dopamine, noradrenaline
Exercise has beneficial effects on hippocampal neural functions. Our previous studies revealed exercise, even in light intensity, activates hippocampal neurons and enhances the hippocampal neurogenesis and memory task performance, however, the neuronal mechanism is still undetermined. We thus aimed to elucidate the neural circuit underlying the light intensity exercise-induced hippocampal activation and memory enhancement. In adult Long Evans male rats with treadmill running at different speeds (light: 15 m/min, severe: 25 m/min, rest: 0 m/min), we monitored monoamine release dynamics in dorsal hippocampus by in vivo microdialysis method. Dopamine (DA) and noradrenaline (NA) release except serotonin (5-HT) were found to be increased in a running speed dependent manner. Furthermore, immunohistochemical analysis showed even light intensity exercise activated tyrosine hydroxylase positive (TH+) neurons in ventral tegmental area (VTA) and locus coeruleus (LC), the main source of DA and NA, respectively, meanwhile exercise did not affect dorsal and median raphe 5-HTergic neurons. Finally, retrograde tracing study revealed that dorsal hippocampus projecting TH+ neurons in LC, but not in VTA, were activated by light intensity exercise. These results provide evidence supporting the hypothesis that light intensity exercise stimulates LC-dorsal hippocampal pathway and might evoke DA and NA co-release from LC. Therefore, LC co-releasing DA and NA may be involved in light intensity exercise-induced beneficial modulations of hippocampal neuronal functions. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-229
Odor presentation in the dorsal and ventral hippocampus
*Anita Banhidi(1), Itaru Imayoshi(1,2,3), Masayuki Sakamoto(1,4)
1. Kyoto University, Graduate School of Biostudies, 2. Faculty Consort of Life and Medical Sciences, Kyoto University, 3. JST CREST, 4. JST PRESTO
Keyword: olfactory discrimination, dorsal hippocampus, ventral hippocampus, go/no-go task
For most organisms, olfaction is a primary source of sensory information. Olfactory information is transmitted to higher brain regions directly or indirectly via the olfactory bulb (OB). However, it is not well understood that how odor information is proceeded and represented in higher brain regions. The hippocampus receives olfactory information from the lateral entorhinal cortex, which receives from the OB and the piriform cortex, and odor stimulation influences the activity of the hippocampus. Also, genetic, anatomical, and functional data suggest that the rodent dorsal and ventral hippocampal CA1 regions (dCA1 and vCA1) play distinct roles. Here, we examined how odor information is represented in the dCA1 and vCA1 regions in the olfactory associated learning. To measure the activity of pyramidal neurons in both dCA1 and vCA1 region during the olfactory associated learning, we performed a go/no-go odor discrimination task with two-photon microscopy under the head-fixed conditions. Genetically encoded green calcium indicator was introduced by adeno-associated virus (AAV2/1-pCaMKII-GCaMP6f) and then implanted with gradient-index (GRIN) lens into the dCA1 and vCA1 regions. By utilizing these techniques, we could observe neural activity in response to odor stimulation from hundreds of neurons simultaneously with single-cell resolution. Chronic calcium imaging during odor-associated learning revealed that the activity of these neurons in both dCA1 and vCA1 regions was changed during the learning process. Furthermore, we found that the odor representation was different between dCA1 and vCA1 regions. Our results identify how the hippocampus encodes the odor information and demonstrate the unique contributions of the dorsal and ventral hippocampus in olfaction. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-230
オペラント学習による前頭皮質内亜領域選択的かつ習熟度特異的なシナプス可塑的変化は仕事中毒様行動の形成に関与する
Region- and proficiency-specific synaptic potentiation in the prefrontal cortex during learning of normal and workaholic-like operant behavior
*浅岡 希美(1)、林 康紀(1)
1. 京都大学大学院医学研究科 システム神経薬理学分野
*Nozomi Asaoka(1), Yasunori Hayashi(1)
1. Dept Pharmacol, Grad Sch Med, Kyoto Univ, Kyoto, Japan
Keyword: Workaholic, Operant learning, Prefrontal cortex
Workaholism is a psychological condition characterized by hard work and compulsive uncontrollable urge to work, suggesting the dysfunction of goal-directed behavior control. Since learning and repetitive performance of tasks are one of the main components of daily work, abnormal memories of working experience may be a cause of workaholism. In the course of learning, task performance is refined and modified through accumulation of the experience. Once established, task performance is stable unless the training conditions is changed, suggesting that long-term memories for task experience define the properties of task performance, such as goal-directedness. However, neural mechanisms for the formation of long-term memories which could affect task performance remain unclear. In this study, we demonstrated that, in mice learning an operant lever pressing task, excitatory synaptic potentiation, assessed by AMPA/NMDA ratio, was transiently induced in several regions of the prefrontal cortex. After the successful learning of lever pressing by random ratio (RR) schedule, training-induced synaptic potentiation was observed in layer 5 pyramidal neurons of the lateral orbitofrontal cortex (OFC) and anterior cingulate cortex (ACC), whereas excitatory synapses on layer 2/3 medial OFC pyramidal neurons were potentiated only in more early stage of learning. When mice were overtrained for additional 4 days by RR schedule, training-induced synaptic potentiation was continuously observed in the ACC. In contrast, when overtraining was performed by random interval (RI) schedule, which could induce workaholic-like task performance in a subset of mice, synaptic potentiation in the ACC was no longer observed. In the lOFC, synaptic potentiation after overtraining was observed only in “workaholic-like” mice. When assessed by devaluation test, RR overtraining did not affect the goal-directedness, whereas RI overtraining significantly decreased the reward-directed score. Consistently, chemogenetic silencing of the ACC disrupted goal-directed action of mice received normal training by RR schedule. These results indicated that, during learning, task-related memories are consolidated in the prefrontal cortex in a region- and proficiency-specific manner. Among the prefrontal cortex, the ACC encodes the memory for goal-directed action, raising the possibility that disruption of continuous updating of task-related memories in the ACC contributes to the expression of workaholism. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-231
嫌悪連想記憶形成の基盤となる神経入力により定義される扁桃体神経細胞群
An input-defined amygdala subpopulation underlying aversive associative memory formation
*春日 優佑(1,2)、Li-Feng Yeh(1)、Joshua Johansen(1,2)
1. 理化学研究所脳神経科学研究センター、2. 東京大学大学院総合文化研究科広域科学専攻生命環境科学系
*Yusuke Kasuga(1,2), Li-Feng Yeh(1), Joshua Johansen(1,2)
1. RIKEN Center for Brain Science, 2. Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo
Keyword: Fear Conditioning, Amygdala, Optogenetics, Fiber Photometry
The ability to form memories of aversive experiences is crucial for animals to avoid future threats and survive. Fear learning is an adaptive process in which animals learn that sensory stimuli predict subsequent aversive outcomes. It is known that cells in the lateral and basal nuclei of the amygdala (LA/B) receive converging sensory and aversive information and that synaptic plasticity in this region is important for fear memory formation. Previously we have found that neurons in the brainstem cuneiform nucleus (CnF) which project to the LA/B convey aversive information to LA/B neurons during auditory fear conditioning. However, the coding properties and functions of LA/B neurons which receive input from the CnF remain elusive. Here, we characterize the neural activity of the LA/B neurons receiving input from the CnF and determine their behavioral functions during auditory fear conditioning in rats. Using in-vivo fiber photometry, we tracked the calcium dynamics of CnF input receiving LA/B neurons during auditory fear conditioning. Preliminary data suggests that fear conditioning increased the responsiveness of these neurons to auditory conditioned stimuli (CS) predicting aversive electrical shock. Furthermore, optogenetic inhibition of the LA/B neurons receiving CnF-input during CS-shock pairings reduced freezing to CS the following day during fear retrieval. These findings support the idea that the subset of the LA/B neurons which receive aversive information from the CnF exhibit learning induced strengthening of auditory processing and control fear memory formation. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-232
Role of Sulfation in Synaptic Plasticity and Memory
*Sharma Shiv(1)、Sahoo Biswaranajn(1)
*Shiv Kumar Sharma(1), Biswaranajn Sahoo(1)
1. National Brain Research Centre, Manesar, Haryana, India
Keyword: synaptic plasticity, long term potentiation, memory, sulfation
It is well established that posttranslational modifications of proteins play critical roles in synaptic plasticity and memory. The role of such modifications including phosphorylation and acetylation has been extensively studied in these processes across different model systems. Long-term potentiation (LTP), a long-lasting enhancement in the synaptic strength in response to an experience, is widely studied as a cellular basis of memory formation. Another prominent protein modification, tyrosine sulfation, plays important roles in several biological processes. However, its role in synaptic plasticity and memory is not well understood. In this study, we studied the role of tyrosine sulfation in LTP and memory. The results show that inhibition of sulfation impairs LTP in the hippocampal slices. In addition, inhibition of sulfation impairs long-term memory. However, inhibition of sulfation spares short-term memory. Further, we found that LTP-inducing stimulus enhances protein tyrosine sulfation. These results suggest that tyrosine sulfation plays an important role in LTP and memory. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-233
バイオレットライトによる中枢神経系を介した認知機能の制御
Violet light modulates the central nervous system to regulate cognitive function
*佐々木 信成(1)、Pooja Gusain(1)、早野 元詞(1,2,3)、菅谷 哲郎(1)、利根川 直也(1)、畑中 悠佑(3)、田村 理佐子(1)、奥山 慧(1)、長田 秀斗(1)、野田 賀大(1)、伴 紀充(1)、満倉 靖恵(2)、Richard A. Lang(4,5)、三村 將(1)、坪田 一男(1,3)
1. 慶應義塾大学医学部、2. 慶應義塾大学理工学部、3. 株式会社坪田ラボ
*Nobunari Sasaki(1), Pooja Gusain(1), Motoshi Hayano(1,2,3), Tetsuro Sugaya(1), Naoya Tonegawa(1), Yusuke Hatanaka(3), Risako Tamura(1), Kei Okuyama(1), Hideto Osada(1), Yoshihiro Noda(1), Norimitsu Ban(1), Yasue Mitsukura(2), Richard A. Lang(4,5), Masaru Mimura(1), Kazuo Tsubota(1,3)
1. Keio Univ Sch of Med, Tokyo, Japan, 2. Fac Sci and Tech, Keio Univ, Yokohama, Japan, 3. Tsubota Lab, Inc., 4. Cincinnati Children's Hosp Med Center, Cincinnati, USA, 5. Univ of Cincinnati, Coll of Med, Cincinnati, USA
Keyword: violet light, opn5, oligodendrocyte, retinal ganglion cell
Sunlight has been utilized evolutionarily as an energy source to produce ATP or as a signal for biological control since before organisms developed eyes. In vertebrates, visible light from 360 nm to 700 nm serves not only a visual function but also a non-visual function such as blue light stimulation regulates sleep, memory, and emotion by melanopsin (OPN4) in intrinsically photosensitive retinal ganglion cells (ipRGCs). Neuropsin (OPN5) is the most recently identified non-visual opsin. OPN5 is a Gi-type G protein-coupled receptor (GPCR) proved to be a visible violet light (VL) responsive opsin (λmax = 380 nm). Mammalian OPN5 contributes to photoentrainment to light/dark (LD) cycle and is also implicated in the local circadian photoentrainment in retina, cornea and skin. Additionally, OPN5 expression in warm-sensing neurons in the hypothalamic preoptic area (POA) was shown to regulate VL-evoked suppression of thermogenesis in brown adipose tissue (BAT). Although OPN5 is also expressed in RGCs, its expression does not overlap with OPN4-positive ipRGCs. We therefore hypothesized that RGCs expressing OPN5 would project to brain regions different from those expressing OPN4 in response to VL stimulation and would have different impacts on brain functions such as memory.
Here, we show that VL stimuli improves cognitive function in aged mice and simultaneously increases neural architecture-related genes such as the maturation of oligodendrocyte-related genes in the hippocampus. In addition, cFos activation is observed at the hippocampus in response to VL stimulation. Tracer experiments identify that VL stimuli received by OPN5-positive RGCs are transmitted to the habenula brain region. Taken together, the results indicate that violet light signals are transmitted from RGCs to the hippocampus presumably through habenula region, and modulate cognitive function by stimulating the maturation of oligodendrocyte precursor cells that promote myelin formation in the hippocampus of aging mice. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-234
Reactivation of task-related cell assembly activity in the prefrontal cortex during non-REM sleep
*Ross J. Purple(1), Aleks P. F. Domanski(1), Matthew W. Jones(1)
1. School of Physiology, Pharmacology & Neuroscience, University of Bristol, UK
Keyword: sleep, cell assembly, neuropixels, reactivation
Introduction: Cell assemblies are groups of neurons that temporally and functionally organise to encode and store information. Convergent evidence shows that neural patterns of awake activity are replayed during non-REM sleep, likely reflecting aspects of memory consolidation. While the coordinated activity between thalamocortical oscillations including slow waves (0.5-4Hz) and spindles (10-15Hz) has been correlated with improvements in learning after sleep, how this links to the processing of specific information across networks of distributed cell assemblies remains unclear.
Methods: Using Neuropixels probes chronically implanted into the medial prefrontal cortex (mPFC), we simultaneously recorded from hundreds of neurons in freely behaving rats. Recordings encompassed more than eight days of learning a spatial alternation task, with each session flanked by pre- and post-task periods of sleep. Principal component analyses were combined with cell assembly detection algorithms to evaluate how cell assemblies spanning the mPFC process spatial, rule and reward information during sleep.
Results: We identified cell assemblies that bridged diverse temporal and anatomical scales, spanning between 20um to over 3000um across deep layers of the cingulate, prelimbic and infralimbic cortices. These assemblies showed striking variation between pre-task rest, task, and post-task rest periods with a preponderance of assemblies identified at longer timescales (>100ms bins) during post-task rest. As animals became more experienced on the task, increasingly strong post-task reactivation of awake activity during non-REM sleep coincided with a greater increase in reactivation compared to pre-task sleep. Reactivation was strongest during sleep spindle oscillations and was related to the degree of coupling between spindles and slow waves.
Conclusions: These initial findings reveal the emergence of reactivation across distributed ensembles of mPFC neurons during spindles and further evidence the importance of coordinated oscillatory activity during sleep for processing previous waking experience. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-235
Neuroprotective Effect of Virgin Coconut Oil and Carvedilol against Doxorubicin-Induced Brain Toxicity and Cognitive Decline in Male and Female Mice
*Azubuike-Osu Sharon(1)、Ezeh Anthonia(1)、Nwaji Azubuike (1)、Biose Ifechukwude (2)
*Sharon Oluchukwu Azubuike-Osu(1), Anthonia Chiamaka Ezeh(1), Azubuike Raphael Nwaji(1), Ifechukwude Joachim Biose(2)
1. Department of Physiology, Alex Ekwueme Federal University Ndufu Alike, Ebonyi, Nigeria, 2. Clinical Neuroscience Research Center, Department of Neurosurgery, Tulane University School of Medicine, USA
Keyword: Neuroprotection, Cognitive function , virgin coconut oil, Carvedilol
Decline in cognitive function is commonly observed after chemotherapy and can impact patients’ quality of life. Women are common sufferers of breast cancer, and sex based impact of doxorubicin-induced brain toxicity with virgin coconut oil and carvedilol supplementation has not been studied yet. We investigated the neuroprotective effects of carvedilol (CARV) and virgin coconut oil (VCO) administered after treatment with doxorubicin (DOX) in mice. Sixty-four young adult male and female BALB/c mice (15-39g) were randomly grouped into control, DOX, DOX + VCO and DOX + CARV groups. All mice received daily treatments by oral gavage for 28 days according to group treatment regimen (n=8): 2 ml/kg b.w of saline, 15 mg/kg b.w of DOX (5th day of every week), 5 ml/kg b.w of VCO (daily) and 5 mg/kg b.w of carvedilol (weekly from days 5-7). Y-maze spontaneous alternation test was used to assess spatial memory on day 28 prior to euthanasia. Brain nitric oxide (NO) levels, iNOS, AchE and TNF-alpha were assessed in all 8 groups. CARV treatment significantly ameliorated decrease in brain weight and improved spatial memory in female mice, when compared to lone treatment with DOX (p<0.05). Also, CARV treatment significantly enhanced brain NO and iNOS levels with a reduction in TNF-alpha expression in male and female mice (p<0.05). Similarly, VCO significantly decreased TNF-alpha and AchE concentrations in both male and female mice. Our results demonstrate the potential neuroprotective benefits of carvedilol and virgin coconut oil treatments after administering doxorubicin chemotherapy which is associated with cognitive dysfunction. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-236
サル脳梁膨大後皮質におけるナビゲーション軌跡の神経表現
Neural representation of navigation trajectories in the monkey retrosplenial cortex
*于 洋(1)、瀬戸川 剛(1,2)、松本 惇平(1,2)、西丸 広史(1,2)、西条 寿夫(1,2)
1. 富山大学 学術研究部 医学系 システム情動科学、2. 富山大学・アイドリング脳科学研究センター
*YU YANG(1), Tsuyoshi Setogawa(1,2), Jumpei Matsumoto(1,2), Hiroshi Nishimaru(1,2), Hisao Nishijo(1,2)
1. System Emotional Science, Faculty of Medicine, University of Toyama, Toyama, Japan, 2. Research Center for Idling Brain Science(RCIBS)・University of Toyama
Keyword: Monkey, Virtual navigation, Retrosplenial cortex, Place responses
Patients or animals with lesions in the retrosplenial cortex (RSC) cannot find their way in familiar environments and cannot draw routes on a 2D map of the familiar environments, suggesting that patients and animals with RSC lesions lack intact allocentric spatial representation to find an appropriate route to a goal. However, it is unknown how RSC neurons represent navigation trajectories in 3D as well as 2D environments. We hypothesized that the ensemble activity of RSC neurons codes routes in both 3D environments and 2D maps. In the present study, monkeys manipulated a joystick in front of a screen and navigated along a figure 8-shaped track to acquire rewards. The mobility area where the monkeys navigated was surrounded by extra-maze distal cues. The monkeys were required to navigate in three types of virtual navigation (VN) tasks from different perspectives: a 3D environment in first-person view, third-person view with a monkey avatar, or an aerial view of the environment with the monkey avatar, which corresponds to route drawing in a 2D map in humans. In each VN task, the monkey alternately navigated two different routes that included overlapping path segments and acquired rewards in the same locations in overlapping path segments. The results indicated that out of 75 RSC neurons, 61 displayed place-related activity (place-related neurons), and 67 neurons showed heading direction-differential activity at least in one of the VN tasks. Furthermore, 42 neurons showed route-dependent activity in the overlapping path segments at least in one of the VN tasks, consistent with an RSC role in the disambiguation of overlapping path segments. In addition, 71 neurons showed neural correlates to reward delivery (reward-related neurons) at least at one of the reward areas in one of the VN tasks, whereas 54 of these 71 reward-related neurons showed route-dependent reward-related activity in the overlapping path segments. The present results provide neurophysiological evidence of trajectory coding in the monkey RSC, consistent with an RSC role in navigation in a familiar environment, and with human imaging studies reporting that the RSC is active during virtual navigation and codes head direction in a large environment. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-237
小型魚類仔魚を用いた全視野刺激への応答行動の比較研究
A Comparative study of repetitive whole-field motion responses in teleost larvae
*磯江 泰子(1)、Luis Hernandez-Nunez(1)、Florian Engert(1)
1. ハーバード大学
*Yasuko Isoe(1), Luis Hernandez-Nunez(1), Florian Engert(1)
1. Harvard University
Keyword: working memory, optomotor response, control theory, teleosts
Ecology diversifies across the earth. Animals in different ecological niches have evolved to be receptive to specific relevant sensory signals, and to optimize the evoked behaviors. Specialized sensory organs have been studied extensively in this context, but few studies have examined how behavioral algorithms and the underlying neural networks have been shaped by such processes. To study this in more detail we selected teleost larvae since they lend themselves readily for behavioral assays, are transparent enough to visualize neurons and have small brains which facilitates whole brain analysis. Here we used two fish model species, zebrafish (Danio rerio) whose natural habitat are non-transparent stagnant waters and medaka fish (Oryzias latipes) who inhabits clear water with faster flow. We show that a subset of whole-field motion stimuli evoke differential responses both in the spatial and temporal domain. First, the size of visual receptive field was found to be larger in medaka. Second, zebrafish respond to 100ms flickering dots, while medaka only reacts to dots that persist for a few seconds (short-term working memory). Finally, zebrafish refresh their visual memory at short time constants, while medaka adapt their behavior after repetitive stimulation with time instants of minutes (long-term working memory). Modeling behavioral algorithm suggests that medaka have two temporal filters at different time scales. The generation of GCaMP transgenic lines allows us to dissect brain regions and neural circuits which are responsible for such temporal filtering processes. This study sheds light on behavioral diversity in ecological contexts and illustrates how animal brains implement neural circuits for adaptive behavior. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-238
花に棲むカザリショウジョウバエのテリトリー空間認識
Spatial cognition for territoriality in flower-breeding fruit fly Drosophila elegans
*石川 由希(1)、林 優人(1)、藤井 航平(1)、桂 宗広(1)、田中 良弥(1)、上川内 あづさ(1)
1. 名古屋大学
*Yuki Ishikawa(1), Yuto Hayashi(1), Kohei Fujii(1), Munehiro Katsura(1), Ryoya Tanaka(1), Azusa Kamikouchi(1)
1. Nagoya University
Keyword: Territorial behavior, Vision, Navigation
Territorial behavior is widespread, from mammals to fish and insects. To keep exclusive access to food and reproductive opportunity, they localize themselves in a particular place with expelling intruding competitors. Some animals occupy both food and reproductive opportunity by territoriality, while others occupy only reproduction without food presence. Although the neural mechanisms of food-dependent territoriality have been elucidated, how animals recognize territories food-independently is still poorly understood.
The flower-breeding fruit fly D. elegans males make territories in blooming flowers of morning glory. They are a good model to understand the neural mechanisms of territoriality because of their available genome information, easy breeding and crossing, and the applicability of neurological knowledge of model species D. melanogaster. To understand the neural mechanism of territorial recognition, responsible sensory information needs to be investigated.
To understand how D. elegans recognizes territory, the territorial behavior in the wild was observed. After landing on the flower, the males headed into the flower tube and stayed there with expelling other invading males. This suggests that the males recognize the flower tube as a territory.
What sensory system does D. elegans use? We firstly investigated the contribution of antennae, which function in olfactory, auditory, and gravitational senses. Males without antennae showed normal territorial behavior, indicating that these senses are not essential for territory recognition.
We next examined the contribution of vision. Under the visual restriction, the speed of heading and frequency of male-male aggression were decreased. This result suggests that D. elegans uses vision to recognize their territory. To further investigate whether visual information alone is sufficient for territorial recognition, we used artificial fabric flowers as a target. Even in the artificial flowers, males showed normal territorial behavior, indicating that males recognize territories food-independently mainly by sight.
D. elegans makes territory in flower tubes. To examine the necessity of flower tubes on territorial recognition, we used tube-removed artificial flowers as a target. Interestingly, males showed normal territorial behavior even in tube-removed artificial flowers. Thus, the flower tube is not necessary for territory recognition, but the periphery of the flowers likely provides some visual information guiding the flies to their territorial location. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-239
Systematic identification of the brain regions connected with the interpeduncular nucleus in the adult zebrafish brain
*Audrey Kawoon Wong(1), Hitoshi Okamoto(1)
1. RIKEN Center for Brain Science
Keyword: griseum centrale, interpeduncular nucleus, lateral line, directional information
The dorsal habenulo-interpeduncular nucleus circuit is known to mediate winning or losing outcomes in social conflict in zebrafish, and recently, emerging evidence has shown that the interpeduncular nucleus (IPN) is involved in encoding left-right dependent decision making and the selection of directional information. Little is known about the downstream projections of the IPN, and we hypothesised that it may be connected regions of the brain that are functionally involved with navigation and orientation.
To investigate this, we used three neurocircuit tracing approaches: 1) Application of lipophilic carbocyanine dyes to fixed brain tissue; 2) Stereotaxic microinjection of fluorophore-conjugated dextran in live fish; 3) Stereotaxic microinjection of vesicular stomatitis virus expressing a fluorescent protein in live fish. The former two are static tracers which travel in both anterograde and retrograde directions, while the latter is a replicating virus capable of trans-synaptic anterograde propagation along the circuit.
We discovered that the IPN receives input from the anterior lateral line area, and that this projection may be reciprocal. Our tract tracing results suggest that transmission between the lateral line and the IPN may be optimised for a shorter conduction latency to facilitate decision making. We also show that neurons in griseum centrale have axons which extend along the tectobulbar tract and into the torus semicircularis, and onwards to the optic tectum.
Additionally, our results show that the both the dorsal and ventral subregions of the IPN is directly connected to a little-known area termed the vascular lacuna of the area postrema. The presence of catecholaminergic neurons, which contain dopaminergic and noradrenergic cells, in the area postrema suggests that they may function to mediate the social behaviour (i.e. winner and loser effects) of fish following the outcome of fights. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-240
Spatial navigation strategies: how do mice make sense of a T-maze?
*Andreoli Lorena(1)、Tomonaga Sutashu(1)、Wickens Jeff(1)、Tanaka Kazumasa(1)
*Lorena Andreoli(1), Sutashu Tomonaga(1), Jeff Wickens(1), Kazumasa Tanaka(1)
1. Okinawa Institute of Science and Technology - OIST
Keyword: navigation, place learning, response learning, dual-solution plus maze
Animals navigate towards a goal through three different strategies: piloting (when an animal follows a salient sensory cue which leads to a goal location), place strategy (when an animal follows a flexible representation or a cognitive map of the space in which it is navigating), and response strategy (when animals base their navigation in a sequence of actions to go to a specific place). The dual-solution plus maze is a behavioural task designed to probe whether the animal is using a place or response strategy, but the cognitive components leading to these different strategies are not well elucidated. It has been shown is classic studies with rodents that some variables influence the choice in strategy. Mainly the length of training, short training leading to more usage of place strategy and long training, response strategy; and the availability of cues (more homogeneous environments lead to animals using response strategy whereas heterogeneous environments lead to place strategy usage). This project aims to elucidate how environmental and training variables can influence the strategy taken by mice in a dual-solution plus maze. For this we manipulated time of training, the availability of reward during the probe trial, availability of distal cues, and the presence of a salient cue. In a plus-shaped maze, we trained animals to go from one arm (i.e, South) to another (i.e, West) to get a reward. After 5 sessions successfully retrieving the reward in the correct arm for 10 times per session, animals underwent a probe trial starting from the opposite start arm (i.e, North). Animals that went on the first trial to the previously baited arm (West) were called place learners, and animals that made the same body turn as they were in the training, but went to an arm that was not previously baited during training, were using a response strategy. We tested 4 different behavioural setups: 1. Highly homogeneous (HIGH), 2. Moderately homogeneous (MOD), 3. Heterogeneous (HET), and 4. With a salient cue (SAL). We further manipulated length of training (short and long) and availability of the reward during probe trials. In all conditions majority of animals were response learners, which contrast with the literature for both rats and mice that showed that animals undergoing short training are mainly place learners even with manipulation of the setup regarding homogeneity of the cues. Our data suggest that mice mainly rely on response strategy in several different contexts and training schedules, contrary to classic literature on dual-solution plus maze. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-241
海馬における経路初期化表現
Path initiation encoding in the hippocampus
*三重野 華菜(1)、井出 薫(1)、髙橋 晋(1)
1. 同志社大学大学院脳科学研究科
*Kana Mieno(1), Kaoru Ide(1), Susumu Takahashi(1)
1. Grad Sch Brain Sci, Doshisha Univ, Kyoto, Japan
Keyword: TIME CELL, PLACE CELL
In the hippocampus, two types of cells were found: place cells whose firing rate increases only when passing through a specific location, and time cells whose firing rate increases only when a specific moment in the delay time has elapsed. Previous reports suggested that whereas the firing fields of individual place cell have similar width and are uniformly distributed over the environment, the firing fields of individual time cells have different duration and are skewed during the delay period as time cells represent a logarithmically compressed timeline. However, there is still no clear explanation as to why the resolution differs. In the present study, using extracellular 16 tetrodes with a custom-made microdrive, we recorded multiple single-unit activities from hippocampal CA1 of rats running in a rectangular elevated maze with two treadmills on which they have to run during a duration varying at each trial (0-10-20-10s). Unlike hippocampal time cells, firing fields of each cell during the delay period were confined not only at the beginning of the delay duration but also of the subsequent running as if they encode path initiation (PI). Thus, we called the cells “PI cell”. Besides, the firing fields were independently retimed or ceased in response with the delay duration. Moreover, the firing fields at the beginning or end of the delay phase were consistently observed across treadmills located at different locations, suggesting that the PI cells are not categorized as place cells. The running acceleration increased on the beginning of the delay period on the treadmill. However, the firing rate did not correlate with the animal's acceleration. These results suggest that the PI cells are not categorized as time cells. Finally, to ask a question of whether the running distance on the treadmill affect the confined firing fields at the beginning of the delay, we examined the remapping of firing fields on the maze. We could not observe the remapping of firing fields over the entire of task performances, suggesting that the confined firing fields at the beginning of the delay cannot be simply explained by the path integration. Taken together, these results suggest that cell firings confined at beginning of the delay period encode not time or place but PIs, and may have a role in the initialization of path integration by distance traveled. We speculate that the firing fields of PI cells contribute the formation of the logarithmically compressed timeline of hippocampal time cells. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-242
心拍誘発電位とマインドワンダリングの相関
Heartbeat-Evoked Potential Correlates with Mind-Wandering Intensity
*川島 一朔(1)、田中 沙織(1)
1. 国際電気通信基礎技術研究所 脳情報通信総合研究所
*Issaku Kawashima(1), Saori C Tanaka(1)
1. ATR Brain Information Communication Research Laboratory Group
Keyword: Mind-Wandering, Heartbeat-Evoked Potential, EEG
The heartbeat-evoked potential (HEP) is a type of event-related potential that is locked to the peaks of electrocardiogram (ECG) and represents the cortical processing of cardiac signals. Recent studies have revealed that this cardiac processing can be a basis of interoception and various mental processes including consciousness and emotion. Thus, HEP can also relate to diverse psychological experiences.We hypothesized that mind-wandering (MW), a phenomenon in which one’s attention drifts away from the current task and situation, also amplifies HEP. It is known that MW occurs in 30–50% of daily life. This field is therefore of great interest to scientists because of its relation to various psychological issues including mental problems and creativity. MW is known as an internally oriented attentional state, in which the attention shifts towards one’s thoughts and feelings instead of sensory perception from the environment. This internal attention state may recruit an interoception process and modify HEP amplitude. Furthermore, it has been indicated that HEP and the default mode network, which is the primary neural basis of MW, present a similar activation pattern. Thus, we posited that MW intensity correlates with HEP amplitude.To test this hypothesis, we investigated the correlation between HEP and self-reported MW. We measured electrocardiogram (ECG) and in-ear electroencephalogram while participants performed a gradual onset continuous performance task (gradCPT). During the gradCPT, we showed gradual transitions of city and mountain images. Subjects were required to respond rapidly by pressing a button when city images appeared and withhold responses when they saw mountain images that were more infrequently flashed. During the task, thought probes questioning the participants’ momentary attentional state were presented 25 times for each participant. From 33 participants, we extracted 19.5 s of EEG data from 15 trials before each probe, and we calculated the mean amplitude 400–500 ms after the R-peaks. We prepared 25 self-reported MW intensities and the corresponding HEP amplitude for each participant, and calculated each Pearson’s correlation coefficient using 1st (participant) level analysis. After applying Fisher’s transformation, we conducted a one-sample t-test on the correlation coefficients using 2nd (group) level analysis. We found that the correlation coefficients were significantly larger than zero (t = 2.442, p = 0.0205). | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-243
Navigation-guided repetitive transcranial magnetic stimulation (rTMS) over right temporoparietal junction of autism spectrum disorder.
*中村 元昭(1)、Fujino Junya(2)
*Motoaki Nakamura(1), Junya Fujino(2)
1. Showa University, 2. Tokyo Medical and Dental University
Keyword: repetitive transcranial magnetic stimulation, temporoparietal junction, autism spectrum disorder, attention shift
Background: Attention is the initial phase of information processing and thus a neural basis of flexible behavioral adaptation. The right temporoparietal junction (rTPJ) is critical for multisensory integration and processing. Especially, the anterior part of rTPJ is causally involved in attention shift. Although autism spectrum disorder (ASD) exhibits attentional deficits, neuromodulation of the attention networks has not been sufficiently established in neurodevelopmental disorders. Objectives: In this pilot study with a crossover design, we compared the effects on attention of intermittent theta burst stimulation (iTBS), continuous theta burst stimulation (cTBS), and sham stimulation over the anterior rTPJ in ASD. Methods: Data obtained from 12 participants were analyzed [mean age: 31.4 ± 9.7 (SD) years; all males; IQ: 105.5 ± 13.5]. Based on structural MRI data, rTMS was navigated to right anterior temporoparietal junction (TPJ) (55, -44, 18 in MNI coordinates), a hub of the ventral attention network. Neuropsychological test battery, including the Posner Cueing Task (PCT), Symbol Digit Coding test (SDC), and Shifting Attention Test (SAT), were performed before and after each rTMS session. Results: Regarding the SDC outcomes, a repeated-measures ANOVA showed no main effect of stimulation condition. However, we found a significant main effect of time (before vs. after stimulation; F =20.57, p < 0.01) and a significant stimulation condition X time interaction (F = 4.59, p = 0.02). When compared with sham stimulation, the outcome improvements were decreased after cTBS (p = 0.01), but not significantly different between iTBS and sham stimulation (p = 0.12). Regarding PCT and SAT outcomes, there were no significant main effects of stimulation condition, time, or interaction of these factors. Conclusions: The results suggest that cTBS-induced modulation of cortical excitability of the anterior rTPJ affects SDC outcomes in ASD. The SDC outcomes evaluate information processing speed and visuospatial attention, and previous studies have shown that rTPJ plays key roles in these functions. Our results are in accordance with these previous findings and extend these observations to ASD. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-244
個人に合わせたデフォルトモードネットワークの機能的結合は持続的注意の能力を反映する
Functional connectivity of personalized default-mode network tracks sustained attention performance
*板橋 貴史(1)、山下 歩(2)、青木 悠太(1)、青木 隆太(1,3)、太田 晴久(1)、中村 元昭(1)、加藤 進昌(1)、橋本 龍一郎(1,3)
1. 昭和大学、2. （株）国際電気通信基礎技術研究所、3. 東京都立大学
*Takashi Itahashi(1), Ayumu Yamashita(2), Yuta Y. Aoki(1), Ryuta Aoki(1,3), Haruhisa Ohta(1), Motoaki Nakamura(1), Nobumasa Kato(1), Ryu-ichiro Hashimoto(1,3)
1. Showa University, 2. Advanced Telecommunications Research Institutes International, 3. Tokyo Metropolitan University
Keyword: sustained attention, default mode network, resting-state functional connectivity
Sustaining attention over time plays a critical role in everyday behaviors. Given that ability to sustain attention can profoundly impact many other cognitive and sensory functions, identifying its neural mechanisms has been an active area of research. Prior studies have demonstrated the connectome-wide relationship with sustained attention ability. In particular, brain regions involved in the default-mode network (DMN) and dorsal attention network (DAN) have been implicated in fluctuations of sustained attention. However, it is still unclear which functional connectivity (FC) is a key for tracking the fluctuations of sustained attention.
To address this question, we collected fMRI and behavioral data from 27 healthy adult males twice. The second visit was at least four weeks apart from the first visit. Participants underwent an MRI session on the first visit, consisting of resting-state fMRI (R-fMRI), functional localizer, and anatomical scans. We used a numerical N-back task for the functional localizer scan to define subject-specific regions of interest (ROIs). Furthermore, participants performed a gradual-onset continuous performance task (gradCPT) outside the MRI scanner. Participants received the same protocol on the second visit, except for the functional localizer and anatomical scans. The fMRI data were acquired using a 3-T MRI scanner (Siemens, Germany). We preprocessed all the MRI data using Statical Parametric Mapping 12. To characterize FC within the DMN (DMN-FC), we created subject-specific ROIs for precuneus and medial prefrontal cortex by a conjunction of deactivation during the functional localizer scan and a population-based atlas. In this study, we computed d-prime as the sustained attention performance. We performed correlational analyses for each visit. We repeated the same analyses by several conditions as control analyses.
Correlational analyses revealed that personalized DMN-FC exhibited statistically significant positive correlations (p < 0.05, two-tailed) in both visits. Furthermore, the change in the performance between the two visits was also statistically significantly correlated with the changes in the strength of the personalized DMN-FC between the two visits (p < 0.05, two-tailed). On the other hand, population-based DMN-FC exhibited a statistically significant correlation on the first visit (p < 0.05, two-tailed) but not on the second visit (p > 0.16, two-tailed). Furthermore, neither FC between DMN and DAN nor DAN-FC showed statistically significant associations with sustained attention performance (all p > 0.06). These findings suggest that personalized parcellation may capture inter-individual variability in the behavior, and DMN-FC may be a key connection for supporting sustained attention. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-245
EEGを用いた安静時および持続的注意時のデフォルトモードネットワークの機能的結合と注意との関係
Default-mode network’s subnetwork functional connectivity reflects attention tendency at rest and behavioral variability in task: an EEG study
*厳 翔(1)、高橋 徹(2)、伊東 正登(1)、栗原 勇人(1)、大須 理英子(2)
1. 早稲田大学人間科学研究科、2. 早稲田大学人間科学学術院
*Xiang Felix Yan(1), Toru Takahashi(2), Masato Ito(1), Yuto Kurihara(1), Rieko Osu(2)
1. Graduate School of Human Sciences, Waseda University, Saitama, Japan, 2. Faculty of Human Sciences, Waseda University, Saitama, Japan
Keyword: Default mode network, exact low resolution electromagnetic tomography, mind-wandering, sustained attention
Functional magnetic resonance imaging (fMRI) studies of sustained attention have shown a correlation between the default-mode network (DMN) and internally focused cognitive functions, such as stimulus-independent thinking and mind wandering (MW). As well, lapses in attention result from abnormal DMN activation during attention tasks. DMN activity has been widely studied using fMRI, however electroencephalographic (EEG) studies are uncommon, rarely supported by behavioral evidence. Furthermore, a previous study showed that the functional connectivity patterns found in fMRI and EEG are distinct from one another. In this study, we attempted to identify the relationship between resting-state EEG DMN connectivity and attention tendency using questionnaires (QS) (i.e., MW scale and CAARS ADHD scale). Then we attempted to examine the relationship between in-task EEG DMN connectivity and in-task sustained attention. In 29 typically developed participants, we performed exact low-resolution electromagnetic tomography (eLORETA) functional connectivity analyses during the resting state and sustained attention tasks (gradual-onset continuous performance task). As a result, under the eye-closed resting state, there was a positive correlation between spontaneous mind-wandering (MW-S) scores and α-2 (10Hz-12Hz) connectivity of left PCC/Rsp and right mPFC (rrho=0.62, p=0.00037), and right PCC/Rsp and right mPFC (rrho=0.65, p=0.00015). Next, we examined the relationship between in-task DMN connectivity and sustained attention evaluated by the reaction time variability. We found that the reaction time variability was negatively correlated with β2 (24Hz-34Hz) connectivity between left ACC and left temporal lobe (rrho=-0.64, p=0.00016), left ACC and right ACC (rrho=-0.62, p=0.00033), left ACC and left PCC/Rsp (rrho=-0.58, p=0.00098), and left ACC and right PCC/Rsp (rrho=-0.67, p=0.00007). Thus, the performance of the sustained attention task may be stabilized when the left ACC centered β2 connectivity is strong. Our results highlight the significance of the resting state α-2 DMN anterior subnetwork in MW-S that high connectivity reflects higher MW tendency, as identified through QS. Moreover, it was found that left ACC centered β2 EEG connectivity had the strongest positive association with stable behavior. Overall, the results of this study have implications for electroencephalographic attention research and clinical intervention. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-246
抑制性ニューロン樹状突起の形態変化による視覚弁別能力の向上
Dendritic transdifferentiation of inhibitory neurons improved visual discrimination
*侯 旭濱(1)、北山 栄子(1)、崎村 建司(2)、杉山 清佳(1)
1. 新潟大学大学院医歯学総合研究科神経発達学分野、2. 新潟大学脳研究所細胞神経生物学分野
*Xubin Hou(1), Eiko Kitayama(1), Kenji Sakimura(2), Sayaka Sugiyama(1)
1. Dept Neuronal Development, Grad Sch Med, Niigata Univ., 2. Dept Cellular Neurobiology, Brain Research Inst, Niigata Univ.
Keyword: Cortical interneurons, Local circuits, Visual two-choice discrimination task, Multipolar/Bipolar dendrite
The cell-type specific properties and connectivity of inhibitory neurons underlie their ability to spatiotemporally shape information processing. Despite much progress in parsing information on interneuron diversity, the mechanism how specific local circuits are established have not been elucidated. We demonstrated the first determinants that specified dendritic properties via experience-dependent actin organization. Cell-type specific expression and membrane-associated distribution of actin-binding proteins allowed interneurons to select their unique dendritic morphologies from a variety of multipolar and bipolar shapes. Morphological transdifferentiation in the juvenile primary visual cortex (V1) affected thecortical function and plasticity, to enable visual acuity. In analysis of VEPs (visual evoked potentials) to different spatial frequency (0.01-0.6 cycle/degree [c/d]) from control V1, the amplitudes were constantly increased toward lower spatial frequency (to 0.01 c/d). Conversely, morphological transdifferentiation from multipolar to bipolar dendrites significantly facilitated the visual response at the limited range of spatial frequency (0.03-0.05 c/d). In addition, we have also found that dendritic transdifferentiation and enhanced visual responses resulted in improving performance of a two-choice visual discrimination task, in which mice select a target from two grating stimuli with different orientations (0° [target] and 90° [non-target]) for reward. In contrast, performances of visual go/no-go task were not significantly different despite dendritic alternations. Thus, the complexity in the two-choice discrimination task may uncover the ability of dendritic morphology in visual perception and decision making. Therefore, actin organization activated by individual experience modified dendritic morphology and increased the heterogeneity of intracortical circuits to enable functional individuality. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-247
Effects of 6-OHDA induced orbitofrontal dopamine depletion on reversal learning of rats in an attentional set-shifting task
*Li Jay-Shake(1)、Su Yu-Chuan(1)
*Jay-Shake Li(1), Yu-Chuan Su(1)
1. Dept Psy, National Chung-Cheng Univ, Chiayi, Taiwan
Keyword: cognitive flexibility, dopamine, orbitofrontal cortex, attentional set-shifting task
Reversal learning is one of the widely used tests for cognitive flexibility. It measures our ability to change behaviors to conform with new rules when external environmental conditions are changing. Previous studies have shown that the orbitofrontal cortex plays a crucial role in the functioning mechanism of reversal learning. However, which neurotransmitter system in the orbitofrontal cortex is involved remains controversial. In one of our early studies, we demonstrated that manipulating orbitofrontal dopamine activities could modulate performance of rats in the reversal learning on an attentional set-shifting task. Studies on marmoset, however, have shown that dopamine depletion in the orbitofrontal cortex by 6-hydroxydopamine (6-OHDA), a selective neurotoxin for dopaminergic neurons, had no effects on reversal learning. In the present study, we injected 6-OHDA in the orbitofrontal cortex of rats, and observed their behaviors in an attentional set-shifting task. In the experiments desipramine and pargyline were also applied to protect the norepinepherinergic and serotonergic neurons from 6-OHDA and to enhance the selectivity of dopaminergic terminals to 6-OHDA. We found that injection of 6-OHDA in the orbitofrontal cortex impaired dose-dependently the reversal learning of rats in the attentional set-shifting task. Further analysis on the type of errors during the reversal learning revealed that rats with dopamine depletion made more regressive errors than controls, suggesting that depriving dopamine activity in orbitofrontal cortex might increase the impulsiveness of animals. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-248
エアロバイク運動中における 生理学的・心理学的指標を用いたフロー評価
Flow assessment using physiological and psychological Indicators during aerobic exercise.
*瀧波 慧(1)、中谷 康司(2)、小野 弓絵(3)、村上 慎吾(4)
1. 中央大学大学院理工学研究科、2. 中央大学経済学部、3. 明治大学理工学部、4. 中央大学理工学部
*Satoshi Takinami(1), Yasushi Nakatani(2), Yumie Ono(3), Shingo Murakami(4)
1. Grad Sch Sci and Eng, Univ of Chuo, Tokyo, Japan, 2. Fac Eco, Univ of Chuo, Tokyo, Japan, 3. Fac Sci and Eng, Univ of Meiji, Kanagawa, Japan, 4. Fac Sci and Eng, Univ of Chuo, Tokyo, Japan
Keyword: Flow, exercise, cerebral blood flow, rating of perceived exertion
Flow, as proposed by Csikszentmihalyi, refers to the mental state in which a performer is fully immersed with intense focus, a loss of reflective self-consciousness, a sense of control over activity, and autotelic experience. Although the experience of flow has been reported in various activities, its characterization relies on subjective measurements. Thus, to understand flow objectively, it is important to evaluate the flow state with physiological measures. In the present study, we examined the relationship between subjective flow experience and physiological phenomena by measuring quantitatively flow self-evaluation and objective physiological indicators during an aero bike exercise. Adult participants with exercise experience were asked to answer on a tablet about perceived exertion and flow during a 20-minute aerobike exercise with load change. The participants were asked to pedal for 20 minutes with the goal of a constant pedal rotation rate while increasing the pedal load. They were also asked to answer the rating of perceived exertion (RPE), in which the subjectively perceived intensity of exercise was selected from 15 levels ranging from "very easy" to "very hard", and flow evaluation, in which the subject was asked to select from three options "yes," "no," or "neither" to the questionnaire items concerning flow experience. Physiological indicators (cerebral blood flow and heart rate) were measured by near-infrared spectroscopy and electrocardiography at rest before the start of exercise, during exercise, and during recovery immediately after exercise. It was found that the cerebral blood flow started to increase rapidly from a certain point during the exercise. As the exercise intensity increased, the perceived flow increased and the RPF decreased while the heart rate kept increasing. The results suggest that increase of cerebral blood flow and flow ratings and reduce of perceived exertion occurred on the same timing and the subjects experienced flow when cerebral blood flow increased. Therefore, flow phenomena, which have been based on subjective sensations, can be objectively evaluated, compared, and leveled using physiological indicators. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-249
精神疾患における認知障害に関わる小脳ー視床ー前頭前野回路基盤
Cerebello-thalamo-prefrontal circuits responsible for cognitive dysfunction in psychiatric disorders
*堤 新一郎(1)、林（高木） 朗子(1)
1. 理化学研究所 脳神経科学研究センター
*Shinichiro Tsutsumi(1), Akiko Hayashi-Takagi(1)
1. RIKEN Center for Brain Science
Keyword: Two-photon imaging, Cognitive dysfunction, Psychiatric disorders, Prefrontal cortex
Cognitive dysfunction in psychiatric disorders such as schizophrenia (SZ) is highly treatment-resistant, because the underlying circuit pathogenesis is unclear. Disrupted connectivity in cerebello-thalamo-cortical (CTC) circuits involving cerebellar lobules Crus I/II, dentate nuclei, higher order thalamic nuclei, and prefrontal cortex (PFC) is increasingly recognized as one of the culprits for the dysfunction. However, the cellular resolution neural circuitry mechanisms remain elusive, hindering refinement of therapeutic measures. To address this issue, we combine activity-dependent functional tracing and large-scale two-photon imaging of CTC circuits in psychiatric disease model animals. We use Setd1a hetero knockout (hKO) mice as a genetic SZ model, and a NMDA receptor blocker MK-801 as a pharmacological psychosis model. To quantify cognitive dysfunction in these models, we established two cognitive tasks under a head-fixed configuration amenable to two-photon imaging: a delayed go/no-go (DGNG) task to address working memory, and a go/no-go (GNG) reversal task to address behavioral flexibility. MK-801 acute injection in expert mice disrupted a DGNG performance but not a GNG performance, indicating that acute cortical disruption disables working memory function. Intriguingly, genetic SZ models failed to show overt deficits in DGNG task, suggesting compensatory mechanisms. To probe the circuit deficits in these models, we established activity-dependent functional tracing of thalamus-PFC projections. We also established large-scale two-photon calcium imaging in the PFC; we succeeded in recording activity of >1,000 neurons in a 1.27 x 1.27 mm field of view over 3 months. Functional tracing and chronic large-scale two-photon recordings of CTC circuits from SZ model mice performing cognitive tasks could reveal the circuit mechanisms of cognitive dysfunction in SZ. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-250
Effects of lateral orbitofrontal and medial prefrontal cortex lesions on the acquisition and extinction of DRL schedule-controlled behavior in the rat
*Liao Ruey-Ming(1,2)、Chen Shuo-Fu(1,2)、Yang Yi-Hua(1,2)、Wu Shu-Yi(1)、Wu Shu-Ting(1)、Lu Xi-Yun(1,3)、Lin I-Shung(1,3)
*Ruey-Ming Liao(1,2), Shuo-Fu Chen(1,2), Yi-Hua Yang(1,2), Shu-Yi Wu(1), Shu-Ting Wu(1), Xi-Yun Lu(1,3), I-Shung Lin(1,3)
1. Department of Psychology, National Cheng-Chi University, Taipei, Taiwan, 2. Institute of Neuroscience, National Cheng-Chi University, Taipei, Taiwan, 3. Brain Science Program, National Cheng-Chi University, Taipei, Taiwan
Keyword: operant conditioning, differential reinforcement of low-rate response, schedule of reinforcement, excitotoxic lesion
Prefrontal cortex (PFC) is known to be critically involved in the execution of high-level cognitive functions including behavioral inhibition and timing process. These two processes are thought to be required for operant responses on a differential reinforcement of low-rate response (DRL) schedule, and yet the role of PFC or its subareas in DRL schedule-controlled behavior remains poorly understood. The present study examined functional consequences of manipulating PFC subareas by the functional disconnection and inclusive lesions of lateral orbitofrontal cortex (lOFC) and medial prefrontal cortex (mPFC) on DRL behavior in male rats. The lesions by ibotenic acid were made before behavioral experiments. The rat was first trained to press lever for a water reinforcer (on FR 1 schedule) and then subjected to acquire a DRL 10 sec (DRL 10-s) task for 18 days and then a DRL 15-s task for 10 days. Subsequently, a 4-day extinction protocol was conducted and followed by a recovery test on DRL 15-s schedule, where the reinforcer contingency resumed and run in four sessions intermittently arranged over 12 days. For the results, the rats with functional disconnection between lOFC and mPFC (via a contralateral lesion protocol) did not differ to those of sham controls throughout the tests of DRL behavior. In contrast, the inclusive lesions of lOFC and mPFC significantly impaired the acquisition of a DRL 10-s as compared to sham control. The lesion effect was remained as the interval up-shifted to 15 s. During the extinction, the functional disconnection had no influence, whereas inclusive lesions caused a significant between-group difference. For the recovery test, there was no significant effectiveness detected in either one of lesion manipulations. Together, the results indicate that both of the lOFC and mPFC are required in the acquisition of DRL behavior. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-251
長時間の一過性eスポーツトレーニングが引き起こす認知疲労は主観的疲労感よりも瞳孔径と関連する
Acute prolonged eSport training induces cognitive fatigue associated with pupil diameter rather than the perceived sense of fatigue
*松井 崇(1)、髙橋 史穏(3)、峰 勇仁(3)、安田 駿(3)、松岡 弘樹(1)、吉武 誠二(3)、越智 元太(2)
1. 筑波大学体育系、2. 新潟医療福祉大学健康科学部、3. 筑波大学大学院人間総合科学研究群
*Takashi Matsui(1), Shion Takahashi(3), Yuji Mine(3), Shun Yasuda(3), Hiroki Matsuoka(1), Seiji Yoshitake(3), Genta Ochi(2)
1. Inst of Health and Sport Sci, Univ of Tsukuba, Ibaraki, Japan, 2. Fac of Health Sci, Niigata Univ of Health and Welfare, Niigata, Japan, 3. Grad Sch Comp Hum Sci, Univ of Tsukuba, Ibaraki, Japan
Keyword: COGNITIVE FATIGUE, EXECUTIVE FUNCTION, PUPIL, ESPORT
eSport, the competitive video game, has emerged worldwide as a new sport, and many young people often play for a long duration as entertainment and self-actualization. Acute and chronic video games played in a moderate period enhance cognitive functions, in particular executive functions. Still, acute prolonged visual display terminals works and mental activities cause a decline in executive functions, called “cognitive fatigue,” with a reduction in pupil diameter as an indirect indicator of prefrontal activity. However, the development of cognitive fatigue due to eSport play and its neurobiological indicators are largely unknown. We here test the hypothesis that prolonged eSport playing causes cognitive fatigue in association with pupil diameter reduction. Nine young males who like video game play wore heart rate monitors and blood glucose sensors, and then underwent 180 min of eSport training (against the CPU). The game title was eFootball (Konami Digital Entertainment, Inc.). Mood (perceived sense of fatigue, enjoyment, and arousal levels, etc.) and executive functions (flanker task, stroop task, and simon task) were assessed at five-time points: pre-playing, 60, 120, 180 min after the start of play, and 30 min after the end of the play. Physiological parameters (heart rate, blood glucose, body temperature, and pupil diameter) were also measured during playing constantly. Perceived sense of fatigue assessed by VAS was significantly increased compared to pre-playing levels only at 180 min. Enjoyment reached a peak at 120 min of play and then recovered to pre levels. Arousal levels measured by the Two-dimensional Mood Scale were increased at 60 and 120 min of play, but declined after 180 min compared to pre levels. Flanker interference was significantly shortened at 60 min of play compared to pre levels, but was delayed at 120 and 180 min. The percentage of correct responses to the flanker task and the surface temperature of the fingertips were decreased only at 180 min. Pupil diameter decreased with playing durations (p = 0.07). Delayed flanker interference did not correlate with a perceived sense of fatigue, but did negatively with changes of pupil diameters from at 60 min of play (Δ pupil diameter). Stroop and simon task performances, heart rate, and blood glucose levels were not changed through the experiment. These results revealed that eSport training over 120 min induces cognitive fatigue, at least in graphic executive functions, in association with a reduction of pupil diameter as a possible biomarker of declined prefrontal activity. Since cognitive fatigue during prolonged eSport playing can diverge from the perceived sense of fatigue, proposing the pupil diameter as a non-invasive neuro-biomarker to aid the perception of cognitive fatigue during eSport playing. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-252
線虫が侵害受容から忌避応答を引き起こす神経回路の解析
Analysis of the neural circuitry that triggers aversive responses occured by nociception in C.elegans
*久世 晃暢(1)、田澤 右京(2)、豊島 有(1)、大江 紗(3)、寺本 孝行(3)、石原 健(3)、飯野 雄一(1)
1. 東京大学大学院理学系研究科、2. 東京大学理学部、3. 九州大学理学系研究院
*Koyo Kuze(1), Ukyo T. Tazawa(2), Yu Toyoshima(1), Suzu Ooe(3), Takayuki Teramoto(3), Ken Ishihara(3), Yuichi Iino(1)
1. School of Science, The university of Tokyo, 2. Faculty of Science, The university of Tokyo, 3. School of Science, The university of Kyushu
Keyword: neural circuit, imaging, nociceptive stimulus, aversive response
神経系は環境情報に基づいて多様な行動を使い分けることができる。そのしくみの理解は神経科学の大きな研究課題のひとつである。線虫（C. elegans）は、すべての神経細胞と互いの接続が同定済みであり、神経活動の観察が容易であることから、こうした神経機構を調べる研究に向いている。線虫は接触、浸透圧、重金属、強い光といった侵害刺激を与えられると、後退や方向転換といった忌避応答を示す。侵害刺激を受容するASH感覚神経と、その下流で忌避行動を引き起こすAVAやAIBなどの介在神経を含む回路図が提案されている。しかし後退や方向転換など多様な忌避応答を引き起こすメカニズムや、特定の神経活動と後退時間やターン確率との定量的な関係は未解明な部分が多く残っている。我々はまず、微小流路内に線虫を固定して侵害刺激を与え、ASH神経が応答することを確認した。さらに自由に動く線虫に対して侵害刺激を与えて、多様な忌避応答が起こることを観察した。次に固定された線虫の頭部全神経を経時的かつ立体的に観察できる4Dイメージング顕微鏡技術を用いて侵害刺激を与えた際の線虫の頭部全神経の活動を観察し、ASHを含むいくつかの神経が刺激に応じて応答していたこと、またAVAなど下流の神経の一部が確率的に応答していたことを確認した。また、塩刺激を与えた線虫の頭部全神経活動データに対して、人工ニューラルネットワーク(NN)モデルや次元削減法を用いて神経網羅的な定量的モデルを構築した。さらに神経活動と行動を結びつけるために、電動ステージを用いて、自由行動中の線虫を自動追尾しながら4Dイメージングを行うトラッキング4Dイメージングの実験系を確立した。今後は、線虫の頭部全神経の活動を行動と同時に記録する。これらのデータをもとに、ASH神経や他の介在神経の活動レベルや内部状態、確率的な要素によってどのような忌避応答が起こるのかを、定量的なシミュレーションにより説明することを目指す。 | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-253
瞳孔拡張は超低強度運動による実行機能向上を予測する：青斑核覚醒系の関与の可能性
Pupil dilation predicts mild exercise-induced higher prefrontal executive function: possible involvement of locus coeruleus arousal system
*桑水 隆多(1,2)、青池 直樹(1)、山崎 雄大(1,2,3)、征矢 英昭(1,3)
1. 筑波大学 運動生化学、2. 日本学術振興会、3. 筑波大学体育系ヒューマン・ハイ・パフォーマンス先端研究センター
*Ryuta Kuwamizu(1,2), Naoki Aoike(1), Yudai Yamazaki(1,2,3), Hideaki Soya(1,3)
1. Laboratory of Exercise Biochemistry and Neuroendocrinology, Univ of Tsukuba, Ibaraki, Japan, 2. Japan Society for the Promotion of Science, Tokyo, Japan, 3. Sport Neuroscience Division, Advanced Research Initiative for Human High Performance (ARIHHP), University of Tsukuba,
Keyword: Exercise, Human locus coeruleus, Executive function, fNIRS
Our previous work has shown that mild aerobic exercise, comparable to casual walking and very slow running, acutely elicits increased dorsolateral prefrontal cortex (DLPFC) activation and improves executive function (Byun et al., NeuroImage, 2014). The exact neurobiological mechanism behind the positive effects of mild exercise remains unclear, but activation of the locus coeruleus (LC) arousal system, which includes catecholaminergic projections to the DLPFC, can be hypothesized as the thus far undetermined mechanism. There is accumulating evidence that non-invasive pupillometry can track the arousal system ascending to the prefrontal cortex from the LC in real time (e.g., Joshi et al., Neuron, 2016; Breton-Provencher and Sur, Nat Neurosci, 2019). The purpose of the present study was to examine whether pupil dilation induced by mild exercise predicts postexercise benefits on executive function. Healthy young adults (19-26 yr) participated in both exercise and resting-control conditions on two separate days. In the exercise condition, participants performed 10 minutes of mild exercise (30%V(・)O2peak) using a cycle ergometer. A Stroop task to assess inhibitory control was performed before and after the exercise, and prefrontal cortical activation during the task was measured using multichannel functional near-infrared spectroscopy (fNIRS). Pupil diameter was measured when each participant looked at a fixation cross before, during, and after exercise. The results revealed that mild exercise significantly elicited pupil dilation, reduction of Stroop interference, and task-related left-DLPFC activation compared with the resting-control condition. In addition, the increased levels of pupil diameter during exercise were significantly correlated with the post-exercise reduction of Stroop interference. This finding strongly supports our hypothesis that the LC arousal system projecting to the prefrontal cortex works during mild exercise and is a possible underlying mechanism of enhanced executive function. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-254
脳波マイクロステートの事象関連変化が、作業記憶プロセスを特徴づける
Event-related dynamics of EEG microstate characterizes working memory function
*玉野 竜太(1,2)、小川 剛史(1)、片桐 愛里沙(1)、蔡 暢(1)、浅井 智久(1)、川鍋 一晃(1)
1. 国際電気通信基礎技術研究所、2. 塩野義製薬株式会社
*Ryuta Tamano(1,2), Takeshi Ogawa(1), Arisa Katagiri(1), Chang Cai(1), Tomohisa Asai(1), Motoaki Kawanabe(1)
1. ATR, 2. Shionogi & Co., Ltd.
Keyword: EEG microstate, event-related dynamics, working memory, cognitive function
EEG microstate, lasting for microseconds and clustered into four classes (A, B, C, and D), is an advanced feature to characterize the spatial/temporal dynamics of electrophysiological activities. It has been hypothesized to be the most basic instantiations of human cognitive processes, named ‘the atoms of thought’ (Lehmann, Machinery of the Mind, 1990). Static microstate parameters, such as averaged duration, occurrence, coverage in resting-state, are reported to alter in several psychiatric disorders (e.g., depressive disorder, autism, and schizophrenia) and during cognitive tasks (e.g., a serial subtraction task, working memory task). However, detailed ‘event-related microstate dynamics’ associated with cognitive function, including working memory (WM), have not been clarified yet. In this study, we examined the event-related microstate dynamics during a WM task (N-back task: 0-, 1-, and 2-back) and its relationship with WM function. Forty-eight healthy adults (25 women, 23 men; age=30.9±10.8) participated in the study. The participants were divided into two groups (high/low-WM performance) based on their N-back performance. The microstate parameters related to the group difference were investigated. In addition, we performed prediction of the WM performance category (high or low) from the microstate transition probabilities with sparse logistic regression (SLR, Yamashita et al., Neuroimage, 2008). Then, we searched time points where the dynamic microstate parameters computed locally around them reflect the individual WM ability. As a result, we found that the specific microstate transition pattern of A→C at 50 to 300 msec after the stimulus onset in the target-trials differed between the two groups (high/low-WM performance) and showed significant correlations with the WM performance indices. Furthermore, as seen in P300 (the response with a positive peak around 300-400 msec after the stimulus onset) and MMN (the response with negative peak to the odd stimulus) during WM tasks, we identified finer changes of the microstate dynamics reflecting the WM performance by considering their polarity, such as the transition pattern of A+→C- (A+/C-: positively/negative correlated spatial map with the representative maps of class A/C) at around 50 to 300 msec after the stimulus. These results demonstrated the event-related fluctuations of the microstate parameters within a fined-tuned short duration represent the WM performance for the first time. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-255
健康な若年成人における身体機能と作業記憶の関係に対する拡散MRIトラクトグラフィーの寄与
Contribution of diffusion MRI tractography to the understanding of the relationship between physical function and working memory in healthy young adults
*宮崎 淳(1)、松田 哲也(2)、石原 暢(3)
1. 早稲田大学グローバルエデュケーションセンター、2. 玉川大学脳科学研究所、3. 神戸大学大学院人間発達環境学研究科
*Atsushi Miyazaki(1), Tetsuya Matsuda(2), Toru Ishihara(3)
1. Global Education Center, Waseda University, Tokyo, Japan, 2. Tamagawa University Brain Science Institute, Tokyo, Japan, 3. Graduate School of Human Development and Environment, Kobe University, Kobe, Japan
Keyword: WORKING MEMORY, PHYSICAL FUNCTION, DIFFUSION MRI
The influence of physical function on brain activation during cognitive tasks is observed in different areas depending on the type of physical function. We have previously shown that activation of the frontoparietal network (FPN) and default mode network (DMN) mediates the relationship between working memory performance and submaximal endurance capacity and hand dexterity, respectively (Ishihara et al., 2020). However, it is unclear how the connectivity of cerebral white matter contributes to these associations. This study aims to clarify the role of cerebral white matter fibers in the relationship between physical function and working memory. A total of 1007 participants in the Human Connectome Project were included in the analysis. A correlational tractography analysis was performed using DSI Studio software. Additionally, we analyzed the role of white matter fibers in brain activity in the FPN and DMN. The region of interest was selected based on our previous work. The results showed that the white matter tracts positively correlated with endurance and working memory was in the anterior corpus callosum. On the contrary, the white matter tracts positively correlated with hand dexterity and working memory was in the posterior corpus callosum. Moreover, we found that the anterior corpus callosum was associated with FPN activity, whilst the posterior corpus callosum was associated with DMN activity. These results suggest that submaximal endurance capacity could contribute to working memory via strengthened anterior corpus callosum connectivity coupled with greater activation in the FPN. In contrast, hand dexterity may contribute to working memory via strengthened posterior corpus callosum connectivity and decreased activation in the DMN. Our findings demonstrate that the corpus callosum plays a key role in efficiently transmitting information between brain hemispheres to support physical function and working memory. | | 2022年7月2日 11:00～12:00 宜野湾市民体育館 ポスター会場2
3P-256
ワーキングメモリートレーニングは新しいオリゴデンドロサイトの産生を促し、より良いパーフォーマンスのために必要である
Working memory training stimulates and requires new oligodendrocyte generation
*清水 崇弘(1)、Stuart Nayar(1)、Malte Kaller(2)、Heidi Johansen-Berg(2)、David Bannerman(3)、遠山 稿二郎(4)、William D Richardson(1)
1. University College London (UCL), Wolfson Institute for Biomedical Research、2. University of Oxford, Nuffield Department of Clinical Neuroscience、3. University of Oxford, Department of Experimental Psychology、4. 岩手医科大学 超微形態科学研究部門
*Takahiro Shimizu(1), Stuart Nayar(1), Malte Kaller(2), Heidi Johansen-Berg(2), David Bannerman(3), Koujiro Tohyama(4), William D Richardson(1)
1. University College London (UCL), Wolfson Institute for Biomedical Research, 2. University of Oxford, Nuffield Department of Clinical Neuroscience, 3. University of Oxford, Department of Experimental Psychology, 4. Iwate Medical University, The Center for Electron Microscopy and Bio-Imaging Research
Keyword: Oligodendrocytes, Myelin, working memory
New myelin-forming oligodendrocytes (OLs) continue to be generated in the mouse CNS for at least the first year of life. We have been studying the function of these newly-generated OLs in adults. To prevent differentiation of new OLs from OL progenitors(OPs) without affecting pre-existing OLs or myelin, we knocked out the transcription factor Myelin regulatory factor (MyRF) conditionally in OPs by tamoxifen administration to Pdgfra-CreERT2: MyRF(flox/flox) (MyRF cKO) mice during adulthood. We have found that learning new skills requires new OL and myelin using the running wheel with unevenly spaced rungs (McKenzie et al., 2014 Science). It is still unclear if newly forming OLs are necessary for non-motor learning and/or memory. We tried to address this question using working memory (WM) experiments in rodents as it is known that the WM training and learning new languages in humans changes microstructures in the white matter, and there are publications that imply the OLs’ involvement in the WM processing and learning in mice. We firstly checked their recognition ability and short-term memory using novel object recognition task and object location task and we found that there are no significant differences between the control and the MyRF cKO mice. Then, we challenged them in appetitive WM tasks in the T-maze and the semi-automated radial arm maze. We found that MyRF cKO mice could not perform as well as the control mice in both WM tasks. We next asked whether WM tasks accelerate OL generation in the control mice. It is known that the prefrontal cortex including the anterior cingulate cortex (ACC) is to actively focus attention on the relevant sensory representation, select information and perform executive functions that are necessary to control the cognitive processing of the information in the WM tasks, not to store information in WM. Thus, we have focused on the pathway of WM processing. ACC neurons project through the corpus callosum (CC) and we looked at the area for newly forming OLs during the WM task by labelling newly forming OLs with EdU and OL markers to distinguish from existing OLs. We found that more newly forming OLs were found in the CC area in better performing control mice in proportion to their performances. Taken together, these findings suggest that the efficiency of working memory can be increased by de novo myelination, stimulated by appropriate training. | |
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