Late-Breaking Abstracts

TOP ＞ Late-Breaking Abstracts

Late-Breaking Abstracts

2022年6月30日　13:00～14:00　沖縄コンベンションセンター展示棟　ポスター会場1 1LBA-043 マウス耳介迷走神経電気刺激の文脈的恐怖消去学習に対する効果 The effect of auricular vagus nerve electrical stimulation on contextual fear extinction learning in mice. 國石洋(1)、竹内絵理(2)、関口正幸(2)、山田光彦(1) 1. 国立精神神経医療研究センター　精神保健研究所　精神薬理研究部、2. 国立精神神経医療研究センター　神経研究所　疾病研究第四部 Hiroshi Kuniishi(1), Eri Takeuchi(2), Masayuki Sekiguchi(2), Mitsuhiko Yamada(1) 1. Dept. Neuropsychopharmacology, National Institute of Mental Health, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan, 2. Dept. Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan Keyword: VAGUS NERVE, VAGUS NERVE STIMULATION, FEAR EXTINCTION, FEAR CONDITIONING The afferent vagus nerve carries sensorial information from peripheral organs to brain, and vagal nerve activity could affect emotion and cognitive functions. The vagus nerve stimulation (VNS) has been reported to facilitating effects of fear extinction learning in rats and expected to improve the effectiveness of exposure-based therapy for patients with post-traumatic stress disorder. Anatomical studies have demonstrated that the auricular branch of vagus nerve innervates external ear. Therefore, auricular VNS (aVNS), a concept of the electrical stimulation of auricular vagus nerve through the skin of external ear, is highlighted as non-invasive method for VNS. Interestingly, it has been reported that aVNS have a facilitating effect of fear extinction learning in human. However, mechanisms how aVNS facilitates fear extinction learning remains less understood. In this study, to explore neural mechanism of aVNS on fear extinction, we developed aVNS in behaving mice by electrical stimulation to external ear and examined the effect of contextual fear extinction learning. For aVNS, mice were applied electrical stimulation to auricular concha area. For sham stimulation, auricular helix area was stimulated. First, to examine neural activation by the aVNS, we examined c-Fos immunoreactivity in the nucleus of solitary tract (NTS), which integrates vagal afferents in the brainstem. The aVNS treatment increased the number of c-Fos positive cells in the NTS compared to sham stimulation. Then, we examined the effect of aVNS on the extinction learning of contextual fear. The mice were contextually conditioned by foot-shock and re-exposed to the context with aVNS or sham stimulation on the next day (the extinction session). On the next day of the extinction session (the extinction-retention session), the mice were re-exposed to the context without stimulation. As a result, aVNS treatment decreased freezing response compared with sham treatment during extinction session and extinction-retention session. These data suggested that our aVNS method facilitates fear extinction learning in mice and would be a useful tool to investigate further the mechanism of aVNS in the brain.		2022年6月30日　13:00～14:00　沖縄コンベンションセンター展示棟　ポスター会場1 1LBA-044 飲水によるラット正中視索前核の細胞外グルタミン酸およびGABA量の変化 Alterations in extracellular glutamate and GABA concentrations in the median preoptic nucleus caused by drinking in rats 田中淳一(1)、高橋眞琴(1)、牛込彰彦(2)、假屋勝秀(3)、林泰資(4) 1. 鳴門教育大学大学院、2. 帝京平成大ヒューマンケア、3. シミッククオリテｲマネジメント、4. ノートルダム清心女子大食品栄養 Junichi Tanaka(1), Makoto Takahashi(1), Akihiko Ushigome(2), Katsuhide Kariya(3), Yasushi Hayashi(4) 1. Naruto Univ Educ, Tokushima, Japan, 2. Faclt Human Care, Teikyo Heisei Univ, Tokyo, Japan, 3. Quality Assurance Dept, CMIC Co Ltd, Tokyo, Japan, 4. Dept Food & Human Nutr, Nortre Dame Seishin Univ, Okayama, Japan Keyword: DRINKING, MEDIAN PREOPTIC NUCLEUS, GLUTAMATE, GABA Activation of glutamatergic neurons in the subfornical organ (SFO) drives drinking behavior through their projections to the median preoptic nucleus (MnPO), a site that has also been involved in the modulation of fluid and electrolyte balance. The MnPO receives γ-aminobutyric acid (GABA)ergic neural inputs derived from other brain regions containing the SFO, but the roles of these neurons in drinking responses remain unanswered. In the present study, we investigated whether hypovolemia causes changes in the release of glutamate (Glu) and GABA in the MnPO, and whether water ingestion causes changes in the release of Glu and GABA in the MnPO elicited by hypovolemia, in freely moving rats. We also examined the actions of the GABAergic system on the release of Glu in the MnPO. Normotensive hypovolemia was evoked by subcutaneous injection of polyethylene glycol (PEG). Extracellular concentrations of Glu and GABA were measured using in vivo microdialysis methods and perfusion with the GABA receptor agonists was performed in the MnPO through a microdialysis probe. Subcutaneous application of PEG (15 or 30%, 5 ml) significantly enhanced dialysate Glu concentrations in the MnPO, whereas the PEG treatment slightly decreased the GABA levels. The PEG-induced enhancement of the Glu concentrations in the MnPO was deeply attenuated by water consumption. In contrast, the water consumption significantly increased the GABA concentrations in the MnPO during 40-80 min after the PEG treatment. Perfusion with the GABA_B receptor agonist baclofen (50 μM), but not the GABA_A receptor agonist musicmol (50 μM), decreased dialysate Glu concentrations in the MnPO. The enhanced Glu levels elicited by the PEG treatment were reduced by perfusion with baclofen, but not by muscimol. These findings suggest that the glutamatergic and GABAergic systems in the MnPO may contribute to motivate and suppress drinking, respectively. The data further imply that the GABAergic inhibitory action on the Glu release through GABA_B receptors, that is activated by water consumption, may be one of mechanisms of drive reduction.

2022年6月30日　13:00～14:00　沖縄コンベンションセンター展示棟　ポスター会場1 1LBA-045 アブラコウモリにおけるdistress条件が誘発する内的状態に関する心電図的検討 Electrocardiogram study of internal states evoked by distress condition in Japanese house bat, Pipistrellus abramus 吉野寿紀(1)、平垣内緑(1)、木原幹樹(1)、小林耕太(1)、飛龍志津子(1) 1. 同志社大学大学院生命医科学研究科 Kazuki YOSHINO(1), Midori HIRAGOCHI(1), Motoki KIHARA(1), Kohta I KOBAYASI(1), Shizuko HIRYU(1) 1. Grad Sch Life & Med Sci, Doshisha University, Kyotanabe, Kyoto, Japan Keyword: EMOTION, NAVIGATION, ULTRASONIC, HEARING Bats have an ability known as echolocation, which allows them to perceive their surroundings even in darkness from the echoes of the ultrasonic pulses they emit. This ability has potential applications in the fields of engineering. Bats are also a suitable model animal for auditory experiments because they have a superb hearing ability, enough to perform navigation without relying on vision. Previous studies have revealed the acoustic characteristics of echolocation and the navigation tactics. However, it remains largely unclear how bats perceive ultrasonic calls to communicate with each other or how their emotional states change. In this study, we focused on the empathic abilities of animals and conducted a basic investigation of these abilities based on electrocardiograms, which are a low invasive measure easily applicable to semi-freely moving animals. First, the subject bats, Pipistrellus abramus, were fixed, and physiological responses such as electrocardiogram and body temperature were recorded. Another individual of the same species was gently poked with a cotton swab to evoke a distress call in front of the subject. As our results show, the presentation of the distress behavior increased the heart rate. The response suggests the decrease of parasympathetic nervous system activity. In addition, when the auditory oddball task, which had an echolocation call as a standard stimulus and the distress call as a deviant, was performed, the heart rate tended to increase with the presentation of the deviant stimulus. On the other hand, heart rate did not increase in the oddball task which had flipped standard and deviant stimuli. These results indicate that the bats' response is not caused by sound stimulation but by the distress context. In other words, the distress call increases heart rate and may have an emotional effect on other bats. Also, the simultaneously measured body temperature was positively correlated with the baseline of the heart rate based on the moving average of a few tens of seconds. On the contrary, the instantaneous changes in heart rate were not tightly related to body temperature and might reflect some kind of internal state, such as their emotion. Therefore, the real time heart rate observation is an important parameter for understanding the emotional state of bats.		2022年6月30日　13:00～14:00　沖縄コンベンションセンター展示棟　ポスター会場1 1LBA-046 マウスにおける内側前頭皮質から扁桃体へのフィードフォワード抑制経路 Organization of the feedforward inhibition circuit in the pathway from the medial frontal cortex to the amygdala in mice 川村太一(1)、Paola Alemán Andrade(1)、大原慎也(1)、筒井健一郎(1) 1. 東北大学 Taichi Kawamura(1), Paola Alemán Andrade(1), Shinya Ohara(1), Kenichiro Tsutsui(1) 1. Tohoku university Keyword: medial frontal cortex, amygdala, interneuron, anterograde transsynaptic tracing The projection from the medial frontal cortex (MFC) to the amygdala (AMG) is considered to play an important role in regulating emotion and mood.Previous studies in rodents have suggested that the subregions of MFC, such as prelimbic and infralimbic cortex, have different functions on fear learning and extinction. Such functional differences could result from different circuit organization of the MFC-AMG pathway. It has been hypothesized that the infralimbic cortex facilitates fear extinction through the input to the distinct neural population in AMG such as inhibitory intercalated cells, which are important for inhibitory control over AMG. However, the circuit organization of the feedforward inhibition in the MFC-AMG pathway is still unclear. In this study, we investigated the projection pattern from MFC to inhibitory interneurons in AMG using anterograde transsynaptic tracing technique mediated by two types of adeno-associated virus (AAV). The first AAV, AAV1-hSyn-Cre, can transport anterogradely and spread from presynaptic to postsynaptic neurons to express Cre recombinase. The second AAV, AAV9-hDlx-Flex-GFP, shows Cre-dependent expression of green florescent protein (GFP) under the control of Dlx enhancer, which is specific to GABAergic inhibitory neurons. By injecting these viruses into MFC and AMG respectively, we could selectively label AMG inhibitory interneurons receiving direct input from MFC. Targeting the projection from the prelimbic cortex to AMG in this method, we observed GFP-labeled cells in basal nucleus of AMG, densely in basolateral AMG and moderately in basomedial AMG. In addition, we further identified the cell type of these inhibitory neurons by immunostaining against parvalbumin (PV) and somatostatin (SOM). We observed differences in the proportion of PV- and SOM-positive cells among AMG subnuclei. These results suggest that the projection from MFC to AMG inhibitory interneurons differ among AMG subnuclei. This inhibitory circuit organization in the pathway from MFC to AMG could lead us to better understand the neural mechanism of emotional regulation.

2022年6月30日　13:00～14:00　沖縄コンベンションセンター展示棟　ポスター会場1 1LBA-047 前部島皮質のオキシトシンシグナルは社会的ストレスの伝達を仲介する Oxytocin signaling in the anterior insular cortex mediates transmission of social stress in mice. 中武優子(1)、古家宏樹(1)、井上ー上野由紀子(2)、井上高良(2)、吉澤一巳(3)、山田光彦(1) 1. 国立精神・神経医療研究センター精神保健研究所精神薬理研究部、2. 国立精神・神経医療研究センター神経研究所疾病研究第六部、3. 東京理科大学薬学部疾患薬理学研究室 Yuko Nakatake(1), Hiroki Furuie(1), Yukiko U. Inoue(2), Takayoshi Inoue(2), Kazumi Yoshizawa(3), Mitsuhiko Yamada(1) 1. Dept Neuropsychopharmacol, Natl Inst Mental Health, NCNP, Tokyo, Japan, 2. Dept Biochem & Cell Biol, Natl Inst Neurosci, NCNP, Tokyo, Japan, 3. Lab Pharmacol & Therap, Fac Pharm Sci, Tokyo Univ Sci, Chiba, Japan Keyword: emotional contagion, oxytocin, insular cortex, social defeat stress Emotional contagion is a phenomenon in which emotional expression of one individual cause similar emotional condition in the individuals who observe it. Although research of emotional contagion has been conducted mainly on the transmission of pain and fear, the neural mechanisms of social stress transmission remain to be elucidated. In this study, we used the witnessing social defeat stress (SDS) as a model of social stress transmission and examined the underlying mechanisms. Male C57BL/6J mice were placed into the home cage of aggressive male ICR mice and exposed to attack from the ICR. The observer C57BL/6J mice witnessed the socially defeated conspecific through a transparent partition in the cage for 10 min. First, we found that the numbers of c-Fos-positive nuclei of oxytocin-receptor-expressing neurons were increased in the anterior insular cortex (aIC) of Oxtr-PA-T2A-tdTomato mice after the witnessing SDS. We next examined whether oxytocin is involved in the transmission of social stress. We found that microinjection of an oxytocin receptor antagonist L-368,899 into the aIC prior to the witnessing SDS suppressed the freezing behavior during the session. Prior injection of L-368,899 also decreased the levels of plasma corticosterone after the session. Finally, we examined the involvement of oxytocin signaling in the emotional alteration after the stress exposure. The halorhodopsin (NpHR), which inhibits neuronal activity in response to yellow light, was expressed in the oxytocin receptor-expressing neurons of the aIC in Oxtr-PA-T2A-iCre mice. Interestingly, suppression of oxytocin receptor-expressing neurons during the stress session prevented the subsequent reduction of social behavior and reward sensitivity. Our results suggest that the transmission of social stress and the subsequent emotional and behavioral changes are mediated by oxytocin signaling within the aIC.		2022年6月30日　13:00～14:00　沖縄コンベンションセンター展示棟　ポスター会場1 1LBA-048 恐怖条件付け学習によるミエリン可塑性の扁桃体における解析 Investigation of fear conditioning-induced myelin plasticity in the amygdala 村田裕夢(1,2)、上田修平(1,2)、箕浦健悟(1,2)、堀金慎一郎(1,2)、竹本-木村さやか(1,2) 1. 名古屋大環境医神経系分野I、2. 名古屋大学院医分子神経科学 Hiromu Murata(1,2), Shuhei Ueda(1,2), Kengo Minoura(1,2), Shin-ichiro Horigane(1,2), Sayaka Takemoto-Kimura(1,2) 1. Department of Neuroscience I, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan, 2. Molecular/Cellular Neuroscience, Nagoya University Graduate School of Medicine, Nagoya University, Nagoya, Japan Keyword: amygdala, myelin, fear conditioning, oligodendrocyte Myelin sheath is a phospholipid-rich sheet-like structure of mature oligodendrocytes wrapping around axons and forming insulators, contributing to rapid and efficient conduction of action potential. Recent studies suggested that myelination occurs dynamically in an activity-dependent manner even in adulthood, and is contributed to neural circuit plasticity during motor learning, associative learning, and memory formation. We previously performed RNA sequencing in micro-punch tissues from various amygdala-related subnuclei 24 hours after fear conditioning, and found the lateral subdivision of the central amygdala (CeL)-specific upregulation of myelin-related genes such as Mbp (myelin basic protein) and Plp1 (Proteolipid protein 1). This result was also confirmed by real-time quantitative PCR. Here, we performed immunohistochemical analysis against the oligodendrocyte-marker protein (Olig2) and the myelin-marker protein (Mbp) and confirmed that oligodendrocytes were distributed in the CeL and apparently formed myelin sheath around axons. While the CeL is composed of inhibitory local circuits, it receives inputs from various brain regions, such as the basolateral amygdala, the parabrachial nucleus, and the insular cortex, and plays an important role in fear learning and expression. Thus, we hypothesized that the myelination of axons projecting into the CeL is promoted activity-dependently and is contributed to the associative fear learning. In order to test this hypothesis, we are currently investigating which circuit projecting to the CeL bears myelinated axons and whether the myelination altered after the associative fear learning.

2022年6月30日　13:00～14:00　沖縄コンベンションセンター展示棟　ポスター会場1 1LBA-049 ウィルストレーシングによるマカクザル内側前頭皮質から扁桃体への投射様式 Topographic organization of medial fronto-amygdalar projections in macaque monkeys as revealed by virus tracing 吉野倫太郎(1)、木村慧(2)、田辺創思(2)、アンディチェン(2)、中村晋也(1)、大原慎也(1)、井上謙一(2)、高田昌彦、筒井健一郎(1,3) 1. 東北大学生命科学研究科脳神経システム分野、2. 京都大学ヒト行動進化研究センター統合脳システム分野、3. 東北大学医学系研究科脳神経システム分野 Rintaro Yoshino(1), Kei Kimura(2), Soshi Tanabe(2), Andi Zheng(2), Shinya Nakamura(1), Shinya Ohara(1), Ken-ichi Inoue(2), Masahiko Takada, Ken-Ichiro Tsutsui(1,3) 1. Laboratory of Systems Neuroscience, Tohoku University Graduate School of Life Science, 2. ystems Neuroscience Section, Center for the Evolutionary Origins of Human Behavior, Kyoto University, 3. Laboratory of Systems Neuroscience, Tohoku University Graduate School of Medicine Keyword: medial frontal cortex, amygdala, neural circuit, emotion The medial frontal cortex (MFC), which includes the anterior cingulate cortex (ACC), is the main source of cortical projections to the amygdala. The interaction between MFC and the amygdala is of special interest, because many clinical studies have reported functional impairments in these structures in patients with depression. It is widely thought that MFC is involved in the regulation of negative emotion and mood, as well as in autonomic responses, via its projections to the amygdala. Based on the cytoarchitectural criteria, MFC and the amygdala can be divided into subregions and subnuclei, respectively. Clarifying the topographic projections from MFC to the amygdala may be a key to understand the function of MFC and the pathogenesis of psychiatric disorders related to the dysregulation of negative emotion and mood. Previous studies using conventional neural tracers reported that the projections from MFC to the amygdala originate mainly from the ventral and dorsal regions of ACC (sgACC and dACC, respectively) and terminate within the basal nucleus. While these studies have examined the distribution of cells projecting to the basomedial amygdala (BMA) among the basal nucleus, the cells of origin of projections to the basolateral amygdala (BLA) remain unknown. The present study aimed to comprehensively investigate the distribution patterns of MFC neurons projecting to BMA and BLA by using adeno-associated virus vectors that permit anterograde and retrograde tracings. We found that MFC subregions projecting to BMA and BLA were clearly segregated except for sgACC that projects to both BMA and BLA. Notably, dACC was observed to be separate into the rostral part projecting to BLA and the caudal part projecting to BMA. Our results suggest that these ACC regions may have different roles in the regulation of emotion and mood via the projections to different subnuclei of the basal amygdalar nucleus. [tm1]amygdaloidでもいいが、タイトルに合わせてamygdalarにした。		2022年6月30日　13:00～14:00　沖縄コンベンションセンター展示棟　ポスター会場1 1LBA-050 マウスの社会ストレスは前頭前皮質錐体神経細胞の樹状突起消失に先行して細胞内変性を誘導する Social stress induces subcellular degeneration preceding dendritic loss of prefrontal pyramidal neurons in mice 沼知里(1)、永井裕崇(1)、永井碧(1)、山下朋美(2)、川島祐介(3)、大野伸彦(4)、片岡洋祐(5,6)、三森-清末優子(6)、加藤太朗(2)、古屋敷智之(1) 1. 神戸大学大学院医学系研究科、2. 住友ファーマ株式会社、3. かずさDNA研究所、4. 自治医科大学医学部、5. 理化学研究所JEOL連携センター、6. 理化学研究所生命機能科学研究センター Chisato Numa(1), Hirotaka Nagai(1), Midori Nagai (1), Tomomi Yamashita (2), Yusuke Kawashima (3), Nobuhiko Ohno (4), Yosky Kataoka (5,6), Yuko Mimori-Kiyosue(6), Taro Kato(2), Tomoyuki Furuyashiki (1) 1. Kobe Univ. Dept. Med., 2. Sumitomo Pharma, 3. Kazusa DNA Res. Inst., 4. Jichi Med. Univ., 5. RIKEN-JEOL Collaboration Center, 6. RIKEN BDR Lab. Keyword: STRESS, DEPRESSION, MITOCHONDRIA, ATROPHY In rodents, chronic social stress induces dendritic atrophy of pyramidal neurons in the medial prefrontal cortex (mPFC) that underlies emotional and cognitive disturbances. However, the mechanism remains elusive. Here we visualized social defeat stress-induced dendritic atrophy and subcellular alterations of mPFC pyramidal neurons in male C57BL/6 mice at the ultrastructural level, using expansion microscopy and serial electron microscopy. The chronic stress decreased the total length of apical dendrites and the number of their branches but unaffected each branch length, suggesting the loss of a subset of dendritic branches. Dendritic branches with varicosities also increased. We then analyzed subcellular alterations of mPFC pyramidal neurons after the acute stress, thus preceding the loss of dendritic branches. The acute stress-induced plasma membrane deformation with morphological changes of mitochondria and microtubule disruption in a subset of dendritic branches, but not adjacent ones. These findings show that stress induces subcellular ｄｅｇｅｎｅｒａｔｉｏｎ in a subset of dendritic branches of mPFC pyramidal neurons preceding their loss with chronic stress.

2022年6月30日　13:00～14:00　沖縄コンベンションセンター展示棟　ポスター会場1 1LBA-051 オンコスタチンMの静脈内投与によるうつ様行動の誘発 Induction of depression-like behavior by intravenous infusion of oncostatin M 石津周(1)、三浦佑慈(1)、郷夏海(1)、南雅文(1) 1. 北海道大学大学院薬学研究院医療薬学部門医療薬学分野薬理学研究室 Amane Ishizu(1), Yuji Miura(1), Natsumi Go(1), Masabumi Minami(1) 1. Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Hokkaido, Japan Keyword: Depression, BBB, Cytokine The blood-brain barrier (BBB) plays a crucial role in regulating molecular trafficking from the circulating blood to the brain parenchyma and maintaining central nerve system (CNS) homeostasis. It is reported that BBB dysfunction is associated with several CNS disorders, such as Alzheimer’s disease, Parkinson’s disease, schizophrenia and major depressive disorder. Oncostatin M (OSM) is one of the IL-6 family cytokines, which are reported to regulate BBB functions. In this study, we examined the effect of intravenous infusion of OSM on depression-like behavior and locomotor activity of BALB/c mice (male, 8 weeks old) using tail suspension (TST) and open field (OFT) tests, respectively. OSM (1 µg/100 µL/body) or vehicle (saline) was administered via tail vein. TST was performed 26 or 50 h after infusion. OFT was performed 8 or 24 h after infusion with monitoring rectal temperature before and 2, 4, 6, 8 and 24 h after infusion. Administration of OSM significantly increased immobility time in the TST at 26 and 50 h after infusion (26 h: vehicle (106.8 ± 10.0 s, n = 12) vs OSM (143.9 ± 8.8 s, n = 12), P = 0.0104, unpaired t-test; 50 h: vehicle (86.0 ± 13.1 s, n = 6) vs OSM (126.5 ± 9.9 s, n = 6), P = 0.0338, unpaired t-test)　without changing locomotor activity. Moreover, OSM significantly raised rectal temperature at 6 and 8 h after infusion (6 h: vehicle (37.04 ± 0.07℃, n = 8) vs OSM (37.41 ± 0.07℃, n = 8), P ＜ 0.0001; 8 h: vehicle (37.13 ± 0.06℃, n = 8) vs OSM (37.83 ± 0.10℃, n = 8), P ＜ 0.0001, two-way repeated measured ANOVA followed by the Sidak’s multiple comparisons test). The results demonstrate that elevated levels of blood OSM induces depression-like behavior. We are now planning to examine the effect of OSM on BBB function in vivo using an Evans blue permeability assay.		2022年6月30日　13:00～14:00　沖縄コンベンションセンター展示棟　ポスター会場1 1LBA-052 Chinese herbal formula Xiaoyaosan alleviates chronic stress induced depressed behavior and microglial activation through inhibiting K63 deubiquitination of NLRP3 Yuan Naijun(1,2,3)、Zhu Wenjun(3)、Ma Qingyu(3)、Chen Jiaxu (3) Naijun Yuan(1,2,3), Wenjun Zhu(3), Qingyu Ma(3), Jiaxu Chen(3) 1. Department of , The Second Clinical Medical College, Jinan University (Shenzhen People's Hospital), Shenzhen, China, 2. Integrated Chinese and Western Medicine Postdoctoral Research Station, Jinan University, Guangzhou, China, 3. Formula-Pattern Research Center, School of Traditional Chinese Medicine, Jinan University, Guangzhou, China Keyword: Depression, deubiquitination, NLRP3, microglia BRCA1-BRCA2 complex subunit 3 (BRCC3) is a Lys-63-specific deubiquitinase that has previously been shown to promote inflammasome activation by deubiquitinating NLRP3. We have previously reported that the NLRP3 inflammasome is involved in the pathogenesis of depression, and the classical Chinese Medicine Xiaoyaosan has antidepressant and alleviate neuroinflammation effects, but its molecular mechanism is still unknown. In this study, we first analyzed the transcriptome of a chronic corticosterone-induced rat model of depression by bioinformatics and verified it by molecular biological experiments such as qRT-PCR, western blot and immunofluorescence. The results showed that compared with the control group, the mRNA and protein expressions of BRCC3 in the hippocampus and cortex of the rats in the depressed group were significantly increased, which was accompanied by the elevated expression of NLRP3, caspase-1 and IL-1β. However, Xiaoyaosan can significantly down-regulate the expression of BRCC3, inhibit the NLRP3/ASC/caspase-1 cascade pathway and the expression of IL-1β. It is suggested that Xiaoyaosan may further inhibit BRCC3-mediated NLRP3 deubiquitination and NLRP3 inflammasome signaling cascade by down-regulating the expression of central BRCC3, and reducing the production of pro-inflammatory factors, thereby alleviating depression-like behavior. In addition, we will further screen and verify the compounds in XYS that can target BRCC3 and their specific molecular mechanisms.

2022年6月30日　13:00～14:00　沖縄コンベンションセンター展示棟　ポスター会場1 1LBA-053 SRI-32743, a novel allosteric modulator, attenuates HIV-1 Tat protein-dysregulated dopamine transmission and alleviates the potentiation of cocaine reward in HIV-1 Tat transgenic mice Zhu Jun(1)、Davis Sarah(1)、Strauss Matthew(1)、Jimenez Torres Ana(1)、Ferris Mark(4)、Zhan Chang-Guo(2)、McLauphlin Jay(3)、Ananthan Sam(5)、Augelli-Szafran Corinne(5) Jun Zhu(1), Sarah E Davis(1), Matthew J Strauss(1), Ana Jimenez Torres(1), Mark Ferris(4), Chang-Guo Zhan(2), Jay P McLauphlin(3), Sam Ananthan(5), Corinne E Augelli-Szafran(5) 1. College of Pharmacy, University of South Carolina, Columbia, SC, USA, 2. College of Pharmacy, University of Kentucky, Lexington, KY, USA, 3. College of Pharmacy, University of Florida, Gainesville, FL, USA, 4. School of Medicine, Wake Forest University, Winston-Salem, NC, USA, 5. Department of Chemistry, Southern Research Institute, Birmingham, AL. USA Keyword: dopamine, HIV-1 Tat, transporter, cocaine Cocaine abuse increases the incidence of HIV-1-associated neurocognitive disorders. We have demonstrated that HIV-1 transactivator of transcription (Tat) allosterically modulates dopamine (DA) reuptake through the human DA transporter (hDAT), potentially contributing to Tat-induced cognitive impairment and potentiation of cocaine-conditioned place preference (CPP). This study determined whether a novel allosteric modulator of DAT, SRI-32743, ameliorates the effects of Tat binding to hDAT in PC12 cells expressing wild-type hDAT and alleviates Tat-induced potentiation of cognitive impairment by novel object recognition (NOR) testing and cocaine reward by CPP in inducible Tat transgenic (iTat-tg) mice. SRI-32743 (50 nM) inhibited [³H]DA uptake and [³H]WIN35,428 binding, and decreased the affinity of cocaine inhibiting [³H]DA uptake in combination with cocaine compared to cocaine alone. Moreover, SRI-32743 decreased the cocaine-induced dissociation rate of [³H]WIN35,428 binding and attenuated Tat protein-inhibited [³H]DA uptake and [³H]WIN35,428 binding. Induction of Tat expression in iTat-tg mice by a 14-day administration of doxycycline resulted in a 31.7% reduction of phase 3 recognition index in NOR and a 2.7-fold potentiation of cocaine-CPP compared to the respective vehicle-treated iTat-tg mice. Systemic administration (i.p.) of SRI-32743 prior to behavioral testing ameliorated Tat-induced impairment of NOR (at a dose of 10 mg/kg) and the Tat-induced potentiation of cocaine-CPP (at a dose of 1 or 10 mg/kg). No effect was observed in saline-treated (uninduced) iTat-tg or doxycycline-treated G-tg (Tat-null) mice. These findings validate that Tat and cocaine interaction with DAT can be modulated through a allosteric modulation manner, suggesting a potential therapeutic intervention for HIV-infected patients with concurrent cocaine abuse.		2022年6月30日　13:00～14:00　沖縄コンベンションセンター展示棟　ポスター会場1 1LBA-054 輪回し行動に関連したマウス側坐核内ドパミン遊離 Wheel-running-related dopamine release in the mouse nucleus accumbens 森翠(1)、新垣紗也(1)、南雅文(1) 1. 北海道大学大学院薬学研究院医療薬学部門医療薬学分野薬理学研究室 Aoi Mori(1), Saya Arakaki(1), Masabumi Minami(1) 1. Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Hokkaido University Keyword: wheel-running, dopamine , GRAB_DA Substance and behavioral addictions such as opioids, alcohol, nicotine, and gambling are common health problems that affect both individuals and society. To solve these problems, further studies are needed to elucidate the mechanisms of substance and behavioral addictions. The mesolimbic reward pathway, which includes dopaminergic projections from the ventral tegmental area to the nucleus accumbens (NAc), has been implicated in the pathophysiology of substance abuse disorders. Drugs of abuse, such as cocaine, morphine and methamphetamine increase dopamine (DA) release in the NAc. In this study, we examined wheel-running-related dopamine release in the NAc by a fiber photometry technique using GRAB_DA (G-protein-coupled receptor-activation-based DA), which enables high temporal resolution measurement of DA release. Male C57BL/6J mice were used to record the dopamine release in the NAc shell. The experiment was carried out in the cage separated into two areas by a partition: one area for wheel-running (wheel area), and the other for isolating mice from the running wheel (waiting area). In the training session, mice were put in the experiment cages without a partition for 30 min each day until the number of wheel rotations, which increased day by day, reached a plateau (≥ 8 days). On the day after the training session ended, DA release was measured during the approach to the running wheel. Specifically, the mouse was put into the waiting area, then the partition was removed so that the animal could access the running wheel. DA release was analyzed for 10 s-periods before and after the time point when the partition was removed. DA release increased significantly in the period 0-10 s compared with the period -10-0 s. The results suggest that behavioral addiction may be formed by repeated wheel-running.

2022年6月30日　13:00～14:00　沖縄コンベンションセンター展示棟　ポスター会場1 1LBA-055 海馬CA1細胞の発火活動と鋭波関連リップルは報酬予測と報酬応答を異なって表現する Hippocampal CA1 neurons represent reward prediction and response differently through spike activity and sharp-wave ripples 坂入朋美(1)、川端政則(1)、Alain Rios(1)、金子聡(1)、酒井裕(2)、礒村宜和(1) 1. 東京医科歯科大学医歯学総合研究科、2. 玉川大学脳科学研究所 Tomomi Sakairi(1), Masanori Kawabata(1), Rios Alain(1), Satoshi Kaneko(1), Yutaka Sakai(2), Yoshikazu Isomura(1) 1. Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 2. Brain Science Institute, Tamagawa University Keyword: Hippocampus, Sharp-wave ripples, Reward, Neural circuit The hippocampus plays a crucial role in storing episodic experiences, which may help predict a reward to learn an optimal action operantly. For example, the spike activity of hippocampal neurons increased at multiple rewarded sites in one environment (Gauthier & Tank, 2018), suggesting hippocampal neurons can individually encode the information that brings reward. On the other hand, sharp-wave ripples (SWRs), synchronous oscillatory activity among hippocampal neurons, often occur in a reward-predictable situation as well as reward-consuming situation. However, it remains unknown how hippocampal neurons, individually or populationally, predict and respond to the outcome (reward or not) for the action. To address this issue, we investigated the spike activity of single hippocampal CA1 neurons and their populational SWRs activity regarding reward prediction and response, while rats performed an alternately rewarded reaction task. In this task, they were required to hold pedals and release either of them in response to a go cue tone. Their correct actions were rewarded with sweet water alternately every two times, and thus, they learned to predict reward or no reward before the action in each trial. The hippocampal neurons displayed phasic spike increases not only around the go cue (leading to the action) but also in response to a success cue (with or without reward). The two phasic activities might be functionally related with action preparation/execution and subsequent feedback confirmation of outcome. The action-related activity of individual neurons was either enhanced or attenuated in rewarded trials compared to no-rewarded trials, and the outcome-related activity was varied between them as well. Thus, it is likely that the reward prediction and acquisition diversely modulate the action- and outcome-related activations in single hippocampal neurons. The SWRs also occurred increasingly towards the action onset and once again in response to the success cue. The former occurrence was enhanced by the reward prediction as expected previously. On the contrary, the latter, the SWRs occurring after the reward delivery, was remarkably suppressed in the presence of actual reward delivery. Taken together, this discrepancy indicates that individual neurons and their populational SWRs activity differently convey information on reward prediction and acquisition in the hippocampal CA1 circuit.		2022年6月30日　13:00～14:00　沖縄コンベンションセンター展示棟　ポスター会場1 1LBA-056 匂い嫌悪学習におけるNMDA受容体とドーパミン受容体のシグナルの統合 Integration of NMDA and Dopamine Receptor Signals in olfactory aversive conditioning. 村谷日向子(1,2)、宮下知之(1)、長野慎太郎(1)、松野元美(1)、齋藤実(1) 1. 東京都医学総合研究所、2. 電気通信大学 Hinako Muratani(1,2), Tomoyuki Miyashita(1), Shintaro Nagano(1), Motomi Matsuno(1), Minoru Saitoe(1) 1. Tokyo Metropolitan Institute of Medical Science, 2. University of Electro-Communications Keyword: Classical conditioning, NMDA receptor, Dopamine receptor Pavlovian classical conditioning is established by forward conditioning in which the conditioned stimulus, CS is presented prior to the unconditioned stimulus, US, but not by backward conditioning in which US is presented prior to CS. Although these conflicts are well known psychological phenomenon, underlying molecular and cellular mechanism that prohibits establishment of backward conditioning has yet been unknown. We previously found that the US (electric shock) information for olfactory aversive conditioning is transmitted by glutamate (Glu) that binds to NMDA resceptor (NR) in the mushroom body (MB). On the other hand, dopamine, which is essential for the establishment of associative learning, is released into the by odor stimulation or electric shock. MB expresses D1 receptors that synthesize cAMP and D2 receptors that inhibit cAMP synthesis, and activation of D1 receptors is essential for the establishment of associative learning. We here found that backward conditioning is established in the transgenic flies that express Mg2+ block mutant NRs or that knocked down dopamine D2 receptor in the MB. Furthermore, intracellular Ca2+ and cAMP concentrations are increased by odor stimulation but not by electrical shock alone in MB. These results suggest that D2 receptors predominate over D1 receptors in US (electric shock) stimulation alone. In line with this, it was suggested that association learning was not established in retrograde conditioning due to the dominance of D2 receptors. This suggests that intracellular Ca2+ changes mediated via NMDA receptors regulate dopamine signaling.

2022年6月30日　13:00～14:00　沖縄コンベンションセンター展示棟　ポスター会場1 1LBA-057 セロトニン5-HT_2C受容体が恐怖記憶の制御に果たす役割及び恐怖記憶の個別要素への再曝露による記憶消去障害効果 The roles of serotonin 5-HT_2C receptor in fear memory and the extinction-disruptive effects of the separate re-exposure to individual components of a complex fear memory 大村優(1)、Bouchekioua Youcef(1,2)、根深真央(1) 1. 北海道大学大学院医学研究院 Yu Ohmura(1), Youcef Bouchekioua(1,2), Mao Nebuka(1) 1. Grad Sch Med, Hokkaido Univ, 2. Queens College, City University of New York Keyword: Fear, Serotonin Pharmacological studies have demonstrated that serotonin 5-HT_2Creceptor antagonists attenuate fear responses, indicating that drugs targeting 5-HT_2C receptors could be promising candidates in the treatment of posttraumatic stress disorder (PTSD). To complement pharmacological findings, we used gene knockout (KO) mice and attempted to clarify the roles of the 5-HT_2C receptor in fear memory and responses. In the contextual fear conditioning test, 5-HT_2C receptor KO mice showed less freezing behavior than wild-type littermates. However, the reduction of conditioned freezing could alternatively be accounted for by increased locomotor activity because we observed the higher locomotor activity in 5-HT_2Creceptor KO mice. To resolve this issue, we measured a ratio of fear responses during and before presenting a conditioned stimulus (context or tone) previously paired with a foot shock by utilizing a conditioned licking suppression paradigm. We replicated the attenuating effects of the 5-HT_2C receptor gene KO on fear responses in the conditioned licking paradigm, where the confounding effects of locomotor activity are neutralized. Furthermore, we examined the effects of separate re-exposure to individual components of complex fear memory (i.e., context and tone). The separate re-exposure induced a deficit of contextual fear extinction in both 5-HT_2Creceptor gene KO and wild-type mice. Although further studies are required to elucidate the mechanisms underlying the extinction-disruptive effects, our findings would invite caution in the future assessment of molecular targets and provide a clue to improve the treatment of PTSD.		2022年6月30日　13:00～14:00　沖縄コンベンションセンター展示棟　ポスター会場1 1LBA-058 Cbln1欠損マウスの3レバーオペラント課題の順序学習の障害 Cbln1-knockout mice display an impairment of motor sequence learning assessed by the three-lever operant task 米田貢(1)、菊池ゆひ(1)、柚崎通介(2)、少作隆子(1) 1. 金沢大学医薬保健研究域保健学系リハビリテーション科学、2. 慶應義塾大学医学部生理学 Mistugu Yoneda(1), Yui Kikuchi(1), Michisuke Yuzaki(2), Takako Ohno-Shosaku(1) 1. Dept. Rehab., Fac. Health Sci., Kanazawa Univ, Ishikawa, Japan, 2. Dept. Physiol., Sch. Med., Keio Univ., Tokyo, Japan Keyword: motor sequence learning, cerebellum, Cbln1, lever-pressing In reward-based motor learning, the cortico-basal ganglia circuit and the dopaminergic system play important roles, but the role of the cerebellum has not been fully investigated. In the present study, we examined the possible role of the cerebellum in reward-based motor sequence learning by using the Yoneda three-lever operant task, which has been developed to study several aspects of reward-based motor learning, including sequence learning and reversal learning. We used Cbln1-/- (Cbln1-KO) mice, which display severe reduction of parallel fiber-Purkinje cell synapses, and Cbln1+/+ (WT) mice. In an operant box, the right (A), the center (B) and the left (C) levers were positioned 2, 4 and 2 cm above the floor, respectively. One training session (60 min) was given once a day and five times a week. The three-lever task was preceded by the one-lever task as shaping. In the one-lever task, reinforcement (one 10 mg food pellet) was delivered when the mouse pressed one of active levers. Initially, the number of active levers was set to three. When the mouse pressed the same active lever more than 100 times per session in two consecutive sessions, the lever was inactivated in the subsequent sessions. When all three levers were inactivated, one-lever task was completed. The mouse was then trained to press three levers in the sequence of ABC (three-lever task). We set the interval time restriction (T). If the interval between two lever presses was longer than T, no food reward was delivered. T was first set to 99.9 s, then decreased to 3 s, 2 s, and 1 s. After the mouse completed the three-lever task, the order was reversed to CBA (reverse three-lever task). In the one-lever task, the number of lever presses was slightly lower in Cbln1-KO mice than WT mice. In the three-lever and reverse three-lever tasks, the number of lever presses and the success rate were lower in Cbln1-KO mice than WT mice. The difference in the success rate between WT and Cbln1-KO mice was larger when T was shorter. These results indicate that the reward-based motor sequence learning is impaired in Cbln1-KO mice. Whether this impairment is caused by the cerebellar dysfunction remains to be determined.

2022年6月30日　13:00～14:00　沖縄コンベンションセンター展示棟　ポスター会場1 1LBA-059 海馬－嗅内皮質回路におけるイベント表現タイミング Timing of behavioral event representation in the hippocampal-entorhinal circuit 相馬祥吾(1,2)、大原慎也(3,4)、野々村聡(2,5,6)、吉田純一(2,7)、末松尚史(8)、Pastalkova Eva (9)、酒井裕(2)、筒井健一郎(3)、礒村宜和(2,5) 1. 京都府立医科大学大学院医学研究科細胞生理学、2. 玉川大学脳科学研究所、3. 東北大学大学院生命科学研究科、4. JST さきがけ、5. 東京医科歯科大学大学院医歯学総合研究科、6. 京都大学霊長類研究所、7. アルバートアインシュタイン医科大学神経科学部門、8. ピッツバーグ大学生物工学部、9. パシフィカ・グラデュエイト研究所 Shogo Soma(1,2), Shinya Ohara(3,4), Satoshi Nonomura(2,5,6), Junichi Yoshida(2,7), Naofumi Suematsu(8), Eva Pastalkova(9), Yutaka Sakai(2), Ken-Ichiro Tsutsui(3), Yoshikazu Isomura(2,5) 1. Dept Mol Cell Physiol, Kyoto Pref Univ of Med, Kyoto, Japan, 2. Brain Sci Inst, Tamagawa Univ, Tokyo Japan, 3. Tohoku Univ Grad Sch of Life Sci, Sendai, Japan, 4. PRESTO, JST, Kawaguchi, Japan, 5. Grad Sch of Med and Dental Sci, Tokyo Med and Dental Univ, Tokyo, Japan, Tokyo, Japan, 6. PRI, Kyoto Univ, Aichi, Japan, 7. Dept of Neurosci, Albert Einstein Coll Of Med, New York, USA, 8. Dept Bioeng, Univ of Pittsburgh, Pittsburgh, USA, 9. Dept of Clinical Psychol, Pacifica Grad Inst, Carpinteria, USA. Keyword: when-where-what information, operant learning, multi-unit recording, optogenetics The entorhinal cortex (EC) is the main interface between the hippocampus and the neocortex. Together with the hippocampus, the EC plays a crucial role in processing information from ongoing events i.e., the when-where-what information necessary for episodic memory. This hippocampal-entorhinal circuit has been anatomically investigated in detail. EC neurons in the superficial layers innervate the hippocampus: EC layer II and III neurons send their projections to hippocampal DG/CA3 and CA1, respectively. Since CA1 neurons are innervated by CA3 terminals, signals from the EC would be directly or indirectly integrated/put together within CA1 neurons. In turn CA1 neurons directly or indirectly (via subiculum) send back the signals to the deep layers of EC. This “entorhinal-hippocampal-entorhinal pathway” is considered the main circuit that supports information processing between the hippocampus and the neocortex. Although great progress in this circuit has been made with understanding the where and when—place/grid cells and time cells respectively—a significant gap in our knowledge exists as almost nothing is known about how WHAT information is dynamically processed. In this study, we investigated the timing of neural representation of two distinct behavioral events related to learning in the entorhinal-hippocampal-entorhinal pathway, CA1 and superficial and deep LEC layers. To do so, we adopted the simplest operant task in which outcome (reward) was presented after rats voluntarily moved their forelimb (action) without external instructive cues. We recorded CA1 and LEC neurons extracellularly from rats both prior to and following training in this task. Both CA1 and lateral entorhinal cortex (LEC) neurons develop task-related activities after learning. Among diverse task-related activities, we compared the transient peak activities that represent action and reward and found a distinct difference in the timing of behavioral event representation between CA1 and LEC. CA1 represents action and reward events in close to real-time, whereas both the superficial and deep layers of the LEC showed delayed representation of those events. Our results suggest that subpopulations exist within which CA1 and LEC neurons process the information in a different order from the anatomically defined hippocampal-entorhinal circuit.		2022年6月30日　13:00～14:00　沖縄コンベンションセンター展示棟　ポスター会場1 1LBA-060 好悪の価値情報を持つショウジョウバエキノコ体γ神経における匂い応答様式の解析 Two-photon live imaging of odor-evoked response in valence-encoding mushroom body γ-neurons of Drosophila 阿部崇志(1)、山崎大介(1)、前山有子(1)、多羽田哲也(1)、廣井誠(2) 1. 東京大学定量生命科学研究所、2. 沖縄科学技術大学院大学 Takashi Abe(1), Daisuke Yamazaki(1), Yuko Maeyama(1), Tetsuya Tabata(1), Makoto Hiroi(2) 1. IQB, University of Tokyo, 2. OIST Keyword: Drosophila mushroom body, olfactory associative memory, odor representation, two-photon live imaging In Drosophila, olfactory associative memories are formed in the mushroom body (MB). The MB consists of third-ordered olfactory neurons, called Kenyon cells (KCs), which is divided into three major subtypes (γ, α’/β’, and α/β) that project bifurcated axons into distinct five lobes . The MB axonal lobes are also separated into multiple compartments by differently innervating dopaminergic neurons (DANs). Recent studies have shown that DANs alter the synaptic connectivity between KCs and MB output neurons (MBONs), and indeed, postsynaptic plasticity have been demonstrated by live imaging as the changes of calcium level in several MBONs in specific compartment in vivo. However, it is still unclear whether plasticity is also induced in the presynaptic terminals of MBKCs as calcium level, and if so, such change is optically detectable event or not, even with high resolution imaging with finely defining compartment labelling marker, as well as whole axonal lobe imaging without reference for the compartment. We previously identified that two subpopulations of MB γ neurons, based on Cyclic-AMP Response Element (CRE)-dependent expression, and defined as γCRE-positive and γCRE-negative KCs (γCRE-p and γCRE-n, respectively). Behavioral analyses also revealed that the γCRE-p KCs are required for aversive memory formation and encode negative valence. Conversely, the γCRE-n KCs are required for appetitive memory and encode positive valence. Taking advantages of these our findings and further functionally subdividable gal4 drivers, γCRE-p-split-gal4 and γCRE-n-gal4,　we employed two-color in vivo imaging for multiple compartments with two-photon microscopy. To simultaneously monitor odor-evoked calcium response in precisely defined multiple presynaptic sites, we combined Gal4/UAS binary system for GCaMP expression, with LexA/LexAop system for compartment reference marker expression. We tested six different odors, Methyl cyclohexanol, Octanol, Hexanol, Pentanone, Citronella Oil, and Apple Cider Vinegar, and found distinct odor response in the axons of the γCRE-p and γCRE-n KCs. We also found that difference of internal state (i.e., fed/starved) affected the relative responsiveness of output compartments. Furthermore, characteristic population response pattern was found in cell body imaging of these mutually exclusive γMB neuron cell types. We expect that our finding would be beneficial for testing the presynaptic plasticity during associative learning and memory formation.

2022年6月30日　13:00～14:00　沖縄コンベンションセンター展示棟　ポスター会場1 1LBA-061 線虫C.エレガンスにおける温度情報および匂い刺激の統合を調節する責任遺伝子のスクリーニング Screening of responsible genes that regulate integration of temperature and odor stimuli in C. elegans 邵震華(1)、青木祐樹(1)、武石明佳(1,2) 1. 理化学研究所脳神経科学研究センター、2. 理化学研究所開拓研究本部 Zhenhua Shao(1), Yuki Aoki(1), Asuka Takeishi(1,2) 1. RIKEN CBS, Japan, 2. RIKEN CPR, Japan Keyword: Multi-sensory Integration, Behavior, Chemotaxis, Thermotaxis Organisms are exposed to various stimuli in natural environment. The ability of animals to make right behavioral choices to deal with multiple information is essential to survival. Importantly, behavior is often not a simple output of a response to a single sensory input. To this end, multiple senses were integrated in nervous system to respond to various stimuli appropriately, though such mechanism of sensory integration remains largely unknown. Here, we use C. elegans as a model animal to study sensory integration. C. elegans are known to show various behavioral responses under different environmental stimuli despite its simple nervous system. In addition, C. elegans is self-fertilized so we can obtain a large number of animals with the same genetic background, which makes C. elegans one of the ideal organisms to explore the complicated system. To explore how the nervous system integrates multiple information in C. elegans, we are investigating the mechanisms of sensory integration of attractive odor and temperature. Studies show worms memorize cultivated temperature (T_c) and migrate toward T_c on a temperature gradient. In addition, worms are attracted by isoamyl alcohol (IAA) around T_c. We conducted the integration experiments to expose worms both to odor and temperature stimuli, and found that worms’ interest to an attractive odor, IAA (isoamyl alcohol), depends on their environmental temperature. We have investigated the possibility of the involvement of several neurotransmitters such as serotonin, dopamine, and glutamate in the integration of odor and temperature stimuli. Preliminary results show the contribution of dopamine & serotonin signaling. To further identify the responsible genes and molecules that regulate the integration of IAA and temperature stimuli, we conducted a forward screening and isolated mutants that have defects in the sensory integration. In the future, further functional analysis of candidate genes is expected to understand the detailed molecular mechanism of multisensory integration in the nervous system.		2022年6月30日　13:00～14:00　沖縄コンベンションセンター展示棟　ポスター会場1 1LBA-062 海馬リップル波に伴うV1領域神経細胞の膜電位変動 Membrane potential fluctuations in visual cortical neurons during hippocampal ripples 鮫島華(1)、池谷裕二(1,2,3) 1. 東京大学、2. Beyond AI 研究推進機構、3. 脳情報通信融合研究センター Hana Samejima(1), Yuji Ikegaya(1,2,3) 1. The University of Tokyo, 2. Institute of AI and Beyond, 3. Center for Information and Neural Networks (CiNet) Keyword: RIPPLE, PRIMARY VISUAL CORTEX, HIPPOCAMPUS, WHOLE-CELL PATCH CLAMP Recent evidence shows that the primary visual cortex (V1) is plastic and associated with storage of visual long-term memory. Consolidation of long-term memory is believed to be mediated by sharp-wave ripples, a form of high-frequency field oscillations that are observed in the hippocampus mainly during slow-wave sleep or under anesthesia. Sharp- wave ripples are initiated mainly in the CA3 region and propagate to the neocortex via the CA1 region and the subiculum. Although the hippocampal formation is not monosynaptically connected with the V1, hippocampal ripples modulate V1 neuronal activity, possibly contributing to the memory formation and retention of vision-relevant memory. Indeed, V1 neurons are recruited in sequential reactivation of memory-relevant spikes, as observed in memory replay in the hippocampus. However, because little is known about subthreshold activity in individual V1 neurons during hippocampal ripples. It remained unclear how V1 neurons fire spikes during hippocampal ripples. To address this question, we recorded membrane potentials (Vms) from V1 layer Ⅱ/Ⅲ pyramidal cell of urethane-anesthetized mice using a whole-cell patch clamp technique, together with recording local field potentials (LFPs) from the hippocampal CA1 region, to explore the Vm fluctuations in V1 neurons in response hippocampal ripples. Time series analyses of hippocampal LFPs and V1 neuronal Vm revealed that some, but not all, neurons are briefly depolarized after the ripple onsets. The latencies of the depolarizations relative to the ripple onsets suggest multisynaptic transmission from the hippocampus to the V1, allowing us to estimate how many synaptic steps (or brain regions) mediated the transmission. Our finding will advance our understanding about neuronal mechanisms underlying memory consolidation related to vision.

2022年6月30日　13:00～14:00　沖縄コンベンションセンター展示棟　ポスター会場1 1LBA-063 VTAからのドーパミンがマウスのナビゲーション行動時の学習に与える影響 Effects of dopamine from VTA on learning during navigation behavior in mice. 玉津裕太(1)、高橋陸(1)、畦地裕統(1)、井出薫(1)、髙橋晋(1) 1. 同志社大学大学院脳科学研究科 Yuta Tamatsu(1), Riku Takahashi(1), Hirotsugu Azechi(1), Kaoru Ide(1), Susumu Takahashi(1) 1. Grad Sch of Brain Sci, Doshisha University Keyword: VTA Reward plays an important role for goal-directed behaviors. Dopamine in the reward system is involved in hippocampus-dependent behaviors and in the regulation of hippocampal plasticity. Several lines of evidence suggest that the dopaminergic system provides reward information to the hippocampus and is important for stabilizing the cognitive map in the hippocampus related to reward. It is well known that two sources of dopamine project to the hippocampus: ventral tegmental area (VTA) and substantia nigra pars compacta (SNc). We hypothesized that the neural circuitry between the VTA dopaminergic neurons and dorsal hippocampus influences goal-directed navigational behaviors. 　To elucidate this, we created a circular track that drew on previous studies. There are four food bins, and the mice can receive a reward at only one location bin (fixed task). We analyzed the number of laps and learning efficiency of the mice during this task. Results showed that the mice had a correct response rate of over 80% three days after the start of the experiment, and that the rate remained stable from the next day onward. After dopaminergic neurons in the bilateral VTA of the mice were lesioned using 6-OHDA, the mice performed the fixed task again. The number of laps and learning efficiency were analyzed in the same way. Results showed that the percentage of correct responses was similar to that before the lesion, but the number of laps was decreased. It has been reported that inhibition of D1/D5 dopamine receptors in the dorsal hippocampus (dCA1) inhibits learning of novel reward acquisition rules. To confirm this phenomenon, we performed another task in which the location of a reward was changed by changing the cue objects in the experimental environment (move task) after the VTA was lesioned in mice. Results showed that the percentage of correct responses was below the chance level in the beginning, but gradually the percentage of correct responses increased. The results of these experiments showed a similar trend to those of previous studies that suppressed hippocampal dopamine receptors, but the number of laps was reduced after the lesion. This may be because the VTA projects not only to the hippocampus but also to other regions of the brain. To elucidate the precise causal relationship between the VTA dopaminergic neurons and hippocampus, we will introduce optogenetics manipulation to the VTA dopamine in the hippocampus in the next experiment.		2022年6月30日　13:00～14:00　沖縄コンベンションセンター展示棟　ポスター会場1 1LBA-064 ノンレム睡眠時活動型の細胞とレム睡眠時活動型の細胞は、高速周波数オシレーションや行動に対して異なるモジュレーションを示す NREM-active and REM-active cells in the limbic and cortical regions are differently modulated by fast network oscillations and behaviors 鍛治谷里咲(1,2)、宮脇寛行(2)、水関健司(2) 1. 大阪公立大学大学院医学研究科歯科口腔外科学、2. 大阪公立大学大学院医学研究科神経生理学 Risa Kajiya(1,2), Hiroyuki Miyawaki(2), Kenji Mizuseki(2) 1. Osaka Metropolitan University Graduate School of Medicine, Department of Oral and Maxillofacial Surgery , 2. Osaka Metropolitan University Graduate School of Medicine, Department of physiology Keyword: Sleep, NREM-and REM-active cells, Synaptic homeostasis, Memory consolidation The synaptic homeostasis hypothesis proposes that sleep decreases the synaptic strength that increases during wakefulness. On the other hand, the memory consolidation hypothesis assumes memory acquired during wakefulness is consolidated during the subsequent sleep. Sleep consists of two distinct states, rapid eye movement sleep (REM) and non-REM (NREM). Neuros change their firing activity depending on the brain states; however, it remains poorly understood whether the modulation of firing by sleep states diverse across neurons. Furthermore, the diversity, if any, may be related to synaptic homeostasis and memory consolidation during sleep. To examine how sleep state modulates firings of individual neurons, we analyzed previously obtained 17-hour continuous recordings of single-unit activities and local field potentials in the ventral hippocampus CA1 region (vCA1), prelimbic cortex layer 5 (PL5), and basolateral nucleus of the amygdala (BLA) of fear-conditioned rats. We found that sleep state modulation on firing was considerably diverse across cells; more than half of excitatory cells (63%, 72%, and 76% in vCA1, PL5, and BLA, respectively) fired significantly faster in REM than in NREM. In contrast, smaller fractions of excitatory cells (35%, 21%, and 21% in vCA1, PL5, and BLA, respectively) fired more in NREM than in REM. Both NREM- and REM-active cells decreased firing across sleep in all examined brain regions (vCA1, PL5, and BLA). Sleep is characterized by various network oscillations, such as hippocampal sharp-wave/ripples, cortical spindles and ripples, and amygdalar high-frequency oscillations, and these oscillations strongly modulate neuronal firing. We found that changes in the modulation of firing activity by the network oscillations were significantly different between NREM- and REM-active cells. In addition, REM-active cells enhanced their firing more prominently than NREM-active cells in response to shock presentation and freezing behavior . Our results show that activities of both NREM- and REM-active cells were similarly downregulated across sleep, whereas they were differently modulated by fast oscillations during sleep and behaviors in wakefulness. These results indicate that NREM- and REM-active cells play different roles in memory processing under similar homeostatic regulation of firing during sleep.

2022年6月30日　13:00～14:00　沖縄コンベンションセンター展示棟　ポスター会場1 1LBA-065 切片作成法および観察レベルによってラット海馬台の領域数は変化する Number of subfields of the rat subiculum changes according to the different sectioning and levels of observation 石原義久(1,2,3)、Grosser Sabine(3)、Guinet Alix(3)、Vida Imre(3)、佐藤二美(2)、窪田芳之(1) 1. 生理学研究所、2. 東邦大学、3. ベルリン・シャリテ医科大学 Yoshihisa Ishihara(1,2,3), Sabine Grosser(3), Alix Guinet(3), Imre Vida(3), Fumi Sato(2), Yoshiyuki Kubota(1) 1. Section of EM, National Institute for Physiological Sciences (NIPS), Okazaki, Japan, 2. Anatomy, Sch Med, Univ of Toho, Tokyo, Japan, 3. Institute of Integrative Neuroanatomy, Charité- Universitätsmedizin Berlin, Berlin, Germany Keyword: hippocampal formation, subiculum, memory, PCP4 Subiculum is a main output part of the hippocampal formation and important for learning and memory. In the previous studies, by the immunoreactivities of nitric oxide synthase and Purkinje cell protein 4 as markers to decide subicular division, we revealed that the subiculum consists of at least two regions in the ventral subiculum (vSub) of horizontal sections and one region in the dorsal subiculum (dSub) of sagittal sections. However, recent studies using coronal sections report that dSub also contains two regions. To confirm the hypothesis that this contradiction derived from different sectioning-methods and different levels for observation, immunoreactivities of serial subicular sections were observed at horizontal, coronal, sagittal and transversal planes. As a result, horizontal vSub showed two regions, distal subiculum (Sub1) and proximal subiculum (Sub2), and caudal coronal dSub and septal sagittal dSub showed one region (Sub1) as the previous studies. However, two regions were also observed at the caudal and intermediate levels of coronal sections and lateral sagittal sections. Accordingly, the same dorsal subiculum indicated different number of regions. It suggests the importance to consider the sectioning-method and observation level for the functional and morphological study of the subiculum. Besides, in the transversal sections, dSub and vSub consisted of one region (Sub1) and two regions (Sub1+Sub2), respectively. Sub2 of the transversal sections was located only at the middle and ventral levels and larger at the more ventral level. This distribution pattern corresponded to that of the projection cells to the lateral septum, which is deeply related to the emotional behavior. It suggests that Sub2 is a neural basis for the emotional memory. Furthermore, patch clamp experiments with intracellular biocytin filling made us possible to observe the exact morphology of subicular pyramidal cells in each area and layer. PCP4-positive cells in the superficial layer were morphologically compact and indicated early branching apical dendrite. On the other hand, deep PCP4 cells tended to have a long apical dendritic tree. In addition to these normal type neurons, we found PCP4 cells with a unique form in the deepest cell layer of the Sub2. The PCP4 cells extended a long apical dendrite to the radial direction and a long basal dendrite to the horizontal direction. The unique morphology suggests another function of Sub2 as an information integration center.		2022年6月30日　13:00～14:00　沖縄コンベンションセンター展示棟　ポスター会場1 1LBA-066 知覚記憶時のネットワークダイナミクスにおけるトップダウン皮質入力の生理的役割の解明に向けて Toward understanding the physiological roles of top-down cortical inputs in network dynamics during perceptual learning 大本育実(1)、池田宗樹(2)、小林碧(1)、小田川摩耶(1)、松原智恵(1)、小林憲太(3)、大泉匡史(4)、村山正宜(1) 1. 理化学研究所　脳神経科学研究センター、2. カリフォルニア大学サンフランシスコ校神経科、3. 生理学研究所、4. 東京大学　総合文化研究科 Ikumi Oomoto(1), Muneki Ikeda(2), Midori Kobayashi(1), Maya Odagawa(1), Chie Matsubara(1), Kenta Kobayashi(3), Masafumi Oizumi(4), Masanori Murayama(1) 1. RIKEN CBS, Saitama, Japan, 2. Dept Neurology, UCSF, San Francisco, USA, 3. NIPS, Aichi, Japan, 4. Grad Sch Arts and Sci, Univ of Tokyo, Tokyo, Japan Keyword: two-photon calcium imaging, wide-field imaging, perceptual memory, network Top-down cortical projections from higher-order brain regions to lower regions are essential for perception, decision, and memory consolidation. Such brain functions are under the control of large-scale dynamics in cortical networks. However, how top-down inputs modify cortical network dynamics remains unclear. In this study, we used wide-field two-photon microscopy, FASHIO-2PM (Ota et al., Neuron 2021), to record large-scale neuronal activity before and after memory consolidation and investigate the physiological roles of top-down inputs in cortical network dynamics. DREADD (designer receptors exclusively activated by designer drugs) system was employed to inactivate the top-down inputs from M2 to S1, which contributes to tactile memory consolidation during non-REM sleep (Miyamoto et al., Science 2016). For network analysis, we calculated co-fluctuation, which enables us to quantify the moment-to-moment cooperative activity among neurons. Our analysis revealed that the stability of co-fluctuation was attenuated during non-REM sleep immediately after the floor texture recognition task, which is a period critical for memory consolidation, i.e., the network of cooperative neurons exhibits transient instability upon tactile learning. Furthermore, the inactivation of the M2-S1 top-down projections by DREADD led to the elimination of the transient instability in the network, together with the elimination of the tactile memory. These results suggest that top-down inputs transiently destabilize cortical networks during non-REM sleep, allowing perceptual information to be integrated into the networks and consolidated as a memory.

2022年6月30日　13:00～14:00　沖縄コンベンションセンター展示棟　ポスター会場1 1LBA-067 短期シナプス可塑性を欠損するシナプトタグミン７のショウジョウバエ突然変異体では、パブロフ条件反射の異常が観察される Defective conditioned response during Pavlovian conditioning in Synaptotagmin 7 mutants of Drosophila 櫻井晃(1)、吉原基二郎(1) 1. 国立研究開発法人情報通信研究機構 Akira Sakurai(1), Motojiro Yoshihara(1) 1. National Institute of Information and Communications Technology Keyword: Synaptic plasticity, Pavlovian conditioning, Synaptotagmin, Drosophila Short-term synaptic plasticity is a fast modification in neuronal presynaptic property that can　enhance release strength to drive facilitation or diminish it to promote depression. By electrophysiological analysis at Drosophila embryonic neuromuscular junctions we demonstrated that the Ca²⁺-binding protein Synaptotagmin 7 (Syt7) determines the sign of short-term synaptic　plasticity by controlling the initial probability of synaptic vesicle fusion. Loss of the protein converts the normally observed synaptic facilitation response during repetitive stimulation into synaptic depression. In contrast, overexpression of Syt7 dramatically enhanced the magnitude of facilitation. Thus, we concluded that Syt7 plays a critical role in short-term plasticity. However, significance of Syt7-dependent short-term plasticity in memory formation are still unclear. To correlate synaptic plasticity to memory, we established a novel Pavlovian conditioning protocol that shows feeding-associated learning by a physically fixed animal with optical access to the CNS for observation and optogenetic manipulation¹. In this protocol, a somatosensory signal mediated by rod removal from legs (conditioned stimulus: CS) is associated with feeding behaviors such as proboscis extension induced by sucrose stimulation (unconditioned stimulus: US). Ca²⁺ imaging of a pair of command neurons that induce feeding behaviors　(termed as “feeding neurons”) demonstrated it acquires the responsiveness to the CS during conditioning, with inactivation of the feeding neuron during conditioning suppressing plasticity. These results suggest　conditioning alters signals flowing from the CS into the feeding neuron functioning as a key integrative hub¹. Taking advantage of this experimental system, here we analyzed Syt7 mutants to correlate short-term plasticity to memory. Syt7 null mutant flies severely showed reduced conditioned response, although CS-induced response and US-induced response during conditioning were similar in Syt7 mutant flies to wild type flies. These results suggest that short-term synaptic plasticity controlled by Syt7 plays a crucial role in memory formation during the Pavlovian conditioning. We will examine change in synaptic inputs onto the feeding neuron in Syt7 mutants to further understand the molecular basis of circuit changes underlying memory formation at the single cell level. 1) Sakurai et al. (2021) Curr. Biol. 31, 4163-4171.		2022年6月30日　13:00～14:00　沖縄コンベンションセンター展示棟　ポスター会場1 1LBA-068 マウスの空間記憶形成の日周変化とニューロステロイドによる制御 Diurnal change in spatial memory formation and its regulation by neurosteroids in mice 清水貴美子(1)、池野知子(1)、前畑佳納子(1)、Wang Qiuyi(2)、高尾敏文(2)、深田吉孝(1) 1. 東京大学、2. 大阪大学 Kimiko Shimizu(1), Tomoko Ikeno(1), Kanako Maehata(1), Qiuyi Wang(2), Takao Toshifumi(2), Yoshitaka Fukada(1) 1. Grad Sch Sci, The University of Tokyo, 2. Ins Protein Res, Osaka University Keyword: neurosteroid, spatial memory, diurnal rhythm, dendritic spine The biological clock regulates not only rhythms such as sleep and hormones, but also higher brain functions such as emotion and memory formation in mammals. We found that maintaining spatial memory was most efficient when learning occurred at the beginning of the light period (dawn) in mice, although there was no diurnal change in spatial learning ability. We found that two 7α-hydroxy-neurosteroids synthesized in the hippocampus (7α-hydroxypregnenolone [7α-OH-Preg] and 7α-hydroxydehydroepiandrosterone [7α-OH-DHEA]) are involved in this mechanism of spatial memory maintenance. 7α-OH-Preg and 7α-OH-DHEA are synthesized from cholesterol by a P450 hydroxylase, CYP7B1. Cyp7b1 mRNA was detected widely in the mouse brain with high levels in the hippocampus with diurnal change. We identified the occurrence of 7α-OH-Preg and 7α-OH-DHEA in the mouse hippocampus after Morris’s water maze task at the beginning of the light period by using LC-MS/MS. Cyp7b1 deficiency impaired remote spatial memory, with recent memory mostly unaffected. The hippocampal dendritic spine densities were reduced in Cyp7b1-deficient mice. The spine densities were no more increased by the training in Cyp7b1-deficient mice, although the spine densities in wild-type mice were significantly increased by the training. Furthermore, chronic intracerebroventricular administration of 7α-OH-Preg and 7α-OH-DHEA in Cyp7b1-deficient mice improved the spine density and remote spatial memory performance. Notably, remote spatial memory impaired by Cyp7b1 deficiency was rescued more significantly by administering the mixture of 7α-hydroxylated steroids than the administration of the single neurosteroid. We concluded that the 7α-hydroxylated neurosteroids are required for synaptic remodeling for long-term maintenance of spatial memory in mice (iScience 2020).

2022年6月30日　13:00～14:00　沖縄コンベンションセンター展示棟　ポスター会場1 1LBA-069 線虫C. elegansの塩走性行動における環境ノイズの影響 Effects of environmental noise on chemotaxis behavior of C. elegans 山内直寛(1,3)、豊島有(2)、廣木進吾(2)、飯野雄一(2) 1. 東京大学理学部生物化学科、2. 東京大学大学院理学系研究科生物科学専攻、3. 沖縄科学技術大学院大学 Naohiro Yamauchi(1,3), Yu Toyoshima(2), Shingo Hiroki(2), Yuichi Iino(2) 1. Dept. Biophysics and Biochemistry, Faculty of Science, Univ of Tokyo, Tokyo, Japan, 2. Dept. Biological Sciences, Grad Sch Science, Univ of Tokyo, Tokyo, Japan, 3. Okinawa Institute of Science and Technology Keyword: NOISE, COMPUTATIONAL ETHOLOGY, CHEMOTAXIS, CAENORHABDITIS ELEGANS Existence of noise is common in the environment in which animals live. Noise generally inhibits information transfer, but there are known cases where noise can have a positive effect on organisms. However, it is not clear how environmental noise affects purposeful behaviors such as the chemotaxis behavior of Caenorhabditis elegans. Based on the hypothesis that "C. elegans utilizes noise in its chemotaxis behavior," we clarified how noise from the environment and the random activity of interneurons arising from the noise affect the chemotaxis behavior of C. elegans. First, to determine under what conditions noise can increase salt chemotaxis efficiency, we created a simulation model in which the probability of direction change is determined based on temporal changes in salt concentration and random stimuli. Parameter search revealed that optimal chemotaxis efficiency is achieved when the magnitude of the random stimulus is non-zero over a wide range of sensory receptive sensitivity, indicating that noise of moderate magnitude increases chemotaxis efficiency. Second, to determine the effect of noise on salt chemotaxis experimentally, the tax-4 gene, which is essential for sensory perception, was expressed only in the salt-sensing neuron ASE, which can be regarded as a state in which environmental noise (sensory information other than salt) is eliminated. Random light stimulation of a strain expressing channelrhodopsin in the interneuron AIB can mimic a state in which noise is added. We created a mutant strain by crossing these two strains and examined whether the noise contributes to the promotion of salt chemotaxis. Using the Multi Worm Tracker, which can record the behavior of many nematodes simultaneously, we recorded the time course of the chemotaxis behavior of the wild strain and the mutant strain and found that the mutant strain was indeed less efficient in chemotaxis behavior. Third, to see if the addition of noise promotes chemotaxis behavior, we created a light irradiation system to perform salt chemotaxis assays under random light irradiation and examined the salt chemotaxis behavior of the mutant strains. We found that salt chemotaxis efficiency was improved when ATR, which is necessary for photoactivation of the AIB neuron, was added in animals. By combining the model and experiments, we have shown that noise tends to promote chemotaxis behavior in C. elegans. In the future, we aim to elucidate the mechanism by which noise effects emerge and to clarify whether environmental noise sensed by sensory neurons propagates to the random activity of interneurons consistent with the hypothesis.		2022年6月30日　13:00～14:00　沖縄コンベンションセンター展示棟　ポスター会場1 1LBA-070 The role of CA2 in organizing hippocampal network dynamics Hongshen He(1), Yi Wang(1), Thomas John McHugh(1) 1. RIKEN Center for Brain Science Keyword:* Hippocampal CA2, DREADD, immobility, computational model Spatial navigation critically relies on the hippocampus, a structure that employs both rate and temporal coding to represent an animal’s position in space. Traditionally, research has examined rodent hippocampal activity during three distinct behavioral states, locomotion, sleep, and awake-immobility, providing a framework to precisely match neural correlates with distinct memory processes. Hippocampal CA2, which had been considered merely a transition zone between CA3 and CA1, now has been shown to possess functionality that impacts learning and memory. Recent studies from our lab have uncovered novel functional roles of CA2 in regulating excitatory and inhibitory neuronal balance during locomotion (Boehringer et al., 2017 Neuron) and coordinating temporal and informational precision during sleep (He et al., 2021 Neuron). While data has suggested CA2 neurons can encode for place during awake-immobility (Kay et al., 2016 Nature), how CA2 shapes activity in other hippocampal regions in this state remains unexplored. Here, we applied chemogenetics to transiently silence CA2 pyramidal cells while mice traverse a novel linear environment and asked how CA2 silencing impacts network dynamics when the animal pauses during behavior. The results revealed that: (1) silencing CA2 abolishes the coherence and the causal temporal relationship between CA3 and CA1; (2) a fraction of CA1 pyramidal cells display higher bursting following CA2 silencing, leading to a loss of precision and coordination with ongoing oscillations; and (3) network dynamics during awake-immobility were altered following CA2 inhibition. Further, a novel deep learning convolutional neural network (CNNs) was applied with cross-validation to evaluate network responses with all interaction weights intact or deleted. Consistent with the previous findings, the CNNs further indicate a pivotal contribution of CA2 in organizing the network balance and signaling spatial representation, especially during awake immobility. This work highlights a novel functional role of CA2 in coordinating network dynamics when animals pause during movement, suggesting a new network interaction scheme, specific to experiences occurring in the absence of locomotion.

2022年6月30日　13:00～14:00　沖縄コンベンションセンター展示棟　ポスター会場1 1LBA-071 経頭蓋静磁場刺激によって誘発された自由視覚探索中の半側空間無視 Hemi-inattention induced by transcranial static magnetic stimulation during free visual exploration 髙橋源太郎(1)、北澤茂(1,2,3) 1. 大阪大学大学院生命機能研究科、2. 大阪大学大学院医学研究科、3. 脳情報通信融合研究センター Gentaro Takahashi(1), Shigeru Kitazawa(1,2,3) 1. Graduate School of Frontier Biosciences, Osaka University, Osaka, Japan, 2. Graduate School of Medicine, Osaka University, Osaka, Japan, 3. Center for Information and Neural Networks (CiNet), National Institute of Information and Communications Technology, Osaka, Japan Keyword: HEMI-INATTENTION, tSMS Hemi-inattention, or hemineglect, is a neurological disorder that has been described since the late 19^th century. Studies to date have identified three major regions of interest (ROIs): the right dorsolateral prefrontal cortex (DLPFC), superior temporal gyrus (STG), and inferior parietal lobe (IPL). However, it is still controversial how these three regions are related with different aspects of the disorder. In this study, we aimed to induce hemi-inattention in healthy volunteers by suppressing each of these regions and to compare their influence on gaze distribution during free visual exploration. Forty-eight subjects participated in the study. Each participant was tested before and after a 20-min exposure to a transcranial static magnetic stimulation (tSMS) with a Neodymium magnet (45 mm in diameter, 1T in the center) or a sham metal cylinder placed over one of the three ROIs (F4 of the international 10-20 system for DLPFC, C6 for STG, and P4 for IPL). During each test period, participants were asked to watch short video clips (n = 120, 44 deg x 25 deg) or still pictures (n = 24) of the same size. Gaze positions were recorded at 1000 Hz (Eyelink 1000). The mean of the gaze distribution shifted to the right by 0.82 deg on average when the tSMS was applied to IPL (p = 0.032, n = 8). More interestingly, when we analyzed gaze distribution over the human faces, P4 stimulation caused subjects to focus on the right side of the human face: the mean gaze location shifted to the right by 10% of the total extent of each face (p = 0.036, n = 8). On the other hand, placement of the magnet on the other regions (F4 or C6) did not affect visual search patterns. These results suggest that tSMS on P4 causes a shift of attention to the right in both self- and object-centered coordinates.		2022年6月30日　13:00～14:00　沖縄コンベンションセンター展示棟　ポスター会場1 1LBA-072 Thalamocortical networks integrate features of auditory sensory history Patrick Steven Hosford(1), Hao Mei(1), Hanna Tagomori(1), Miho Nakajima(1), L. Ian Schmitt(1) 1. Laboratory for Distributed Cognitive Processing, RIKEN Center for Brain Science, Wakō, Japan Keyword:* Sensory history, Thalamocortical networks, Decision making In order to usefully interpret sensory information, we must construct a flexible internal model that allows us to compensate for ambiguous and discontinuous inputs. While this model is based, at least in part, on current inputs, it may also incorporate a longer-term “history” that reflects previous statistical regularities. Thalamocortical interactions are emerging as essential for complex aspects of perceptual processing and may work to maintain the sensory history component of the internal model. Here, we investigated how sensory representations in the posterior parietal cortex (PPC) are shaped by its thalamic counterpart the pulvinar nucleus (PUL) and whether these interactions help maintain a “buffer” of recent sensory history which is called upon during decision-making. Using a feature-based auditory decision-making task in mice, we found that optogenetic silencing of either PPC or PUL reduced the influence of experiential history on current decisions. To determine how these circuits might encode history information used in ongoing decision-making, we sought to investigate auditory sensory encoding in the PPC and PUL using a novel auditory oddball protocol. Neuropixels and tetrode-based single unit recordings during oddball sequence presentation revealed preferential responses to both specific stimuli as well as patterns in stimulus presentation suggesting that neuronal activity in both circuits reflects stimulus history. In contrast to the pattern typically observed in early sensory areas, generalized linear modelling (GLM) analysis showed that neuronal responses were suppressed by rare “oddball” tone stimuli relative to more common “non-oddball” tones. Optogenetic inhibition of PUL reversed this non-oddball selectivity and produced substantial remapping of response preferences in PPC. Moreover, suppression impacted PPC network connectivity, suggesting that the PUL may modulate stimulus history encoding by controlling cortico-cortical interactions. To gain further insight, we took advantage of the dense sampling afforded by Neuropixels to isolate cortical layers and identify subtypes of recorded neurons based electrophysiological markers allowing us to assess how each subtype was impacted by PUL suppression. Overall, our results indicate that auditory sensory history is represented across both PPC and PUL and suggest mechanisms by which interactions between these circuits may enable maintenance of this information critical for decision-making.

2022年6月30日　13:00～14:00　沖縄コンベンションセンター展示棟　ポスター会場1 1LBA-073 マーモセットへのGO/NO-GO課題の応用 Go/No-Go task for mapping brain functions in marmoset 中村克樹(1)、眞下久美子(1)、岩沖晴彦(2) 1. 京都大学ヒト行動進化研究センター、2. 量子科学技術研究開発機構 Katsuki Nakamura(1), Kumiko Mashita(1), Haruhiko Iwaoki(2) 1. EHUB, Kyoto University, Inuyama, Japan, 2. National Institutes for Quantum Science and Technology Keyword: marmoset, prefrontal cortex, response inhibition, cognitive function Currently, the Brain/MINDS Project is mapping brain functions in marmosets. The primary reason for targeting the marmoset, a small nonhuman primate, is that it has the well-developed prefrontal cortex that is not found in rodents. However, the appropriate tasks to examine functions of the prefrontal cortex in marmosets have not yet been adequately developed. It is well known that the prefrontal cortex has various important functions, such as working memory, response inhibition, decision making, motivation, etc. In the current study, focusing on response inhibition in particular, we developed a GO/NO-GO task for marmosets and attempted to train them. Two marmosets (8 years old female and 14 years old male), considered to be in their middle-to-older age, were used as subjects. A cognitive experimental apparatus with a touch screen (Takemoto et al., 2011) was used for the present experiment. The experiment was conducted in a cage room between 10:00 and 12:00. In the GO/NO-GO task, a red square (22 mm x 22 mm) was presented at the center of the screen. The marmoset touched the square to initiate the trial. One second after the touch, the red square disappears and a graphic patten (22 mm x 22 mm) as a visual stimulus is presented at the center. We used 3 stimuli: A, B, and C. If A or B was presented, the marmoset was required to touch the stimulus within 2 second (GO trials). If C was presented, the subject was required to avoid touching the stimulus for at least 2.5 seconds (NO-GO trials). First, the subjects were trained with only two stimuli, A and C, and then with three stimuli. The female marmoset learned the GO/NO-GO task, and the correct performance rate was over 85%. The male marmoset was still on the way to learn the task. Here, based on the training procedure and the performance of two middle-aged marmosets. we will discuss the usefulness of the GO/NO-GO task for marmosets.		2022年6月30日　13:00～14:00　沖縄コンベンションセンター展示棟　ポスター会場1 1LBA-074 男子大学生テニス選手におけるサービス精度と主観的運動強度および神経認知機能との関連性 Relevance of perceived exertion and neurocognitive functions on serve accuracy among male university tennis players 黒田裕太(1)、石原暢(2) 1. 北翔大学生涯スポーツ学部スポーツ教育学科、2. 神戸大学大学院人間発達環境学研究科 Yuta Kuroda(1), Toru Ishihara(2) 1. Department of Sport Education, Hokusho University, Ebetsu, Japan, 2. Graduate School of Human Development and Environment, Kobe University, Kobe, Japan Keyword: EXECUTIVE FUNCTION, TENNIS, PERFORMANCE Background and aim: We previously examined the association between time-course changes in neurocognitive functions and the percentage of points won during a tennis singles match (Ishihara et al., 2018). The findings of that study showed that neurocognitive functions during matches were positively correlated with the percentage of points won. However, the study only focused on points won; thus, the possible association between time-course changes in neurocognitive functions and more specific skills remained unclear. Therefore, in the present study. we investigated the associations among time-course changes in ratings for perceived exertion, neurocognitive function, and 2nd serve accuracy during 30-minute tennis training sessions. Methods: The participants were 11 Japanese male tennis players. Neurocognitive function and 2nd serve performance were evaluated using the paper version of the Stroop Color and Word Test (SCWT) (Stroop, 1935) and a serve performance test, respectively. We used the SCWT because previous studies in this field focused on executive functioning (Sakamoto et al., 2018; Vestberg et al., 2012) and the test is widely used to assess this function. Thereafter, the study participants took part in a 30-minute tennis training program. The Pearson correlation was used to determine the relationships among the ratings for perceived exertion, interference scores on SCWT performance, and 2nd serve performance. Results: Higher ratings regarding perceived exertion were correlated with lower serve accuracy (r = −.57, p = .07) and poorer SCWT performance (r = −.65, p = .03) in the posttest. The pre-to-post changes in serve accuracy were positively associated with the changes in SCWT performance (r = .54, p = .08) and SCWT performance in the posttest (r = .73, p = .01). Conclusions: The results of the present study suggest that the time-course changes in neurocognitive function during tennis play are positively associated with the accuracy of the 2nd serve. These findings expand the previous knowledge regarding the positive association between time-course changes in neurocognitive functions and percentages in points won during tennis play to include more specific skills (i.e., 2nd serve accuracy).

2022年6月30日　13:00～14:00　沖縄コンベンションセンター展示棟　ポスター会場1 1LBA-075 ワーキングメモリにおけるアクティブ状態と準アクティブ状態の共存 Co-existence of Active and Semi-active States in Working Memory 出利葉拓也(1)、牛山潤一(2,3) 1. 慶應義塾大学大学院政策・メディア研究科、2. 慶應義塾大学環境情報学部、3. 慶應義塾大学医学部リハビリテーション医学教室 Takuya Ideriha(1), Junichi Ushiyama(2,3) 1. Graduate school of Media and Governance, Keio University, 2. Faculty of Environment and Information Studies, Keio University, 3. Department of Rehabilitation and Medicine, Keio University School of Medicine, Keio University Keyword: NEURAL OSCILLATION, REACTION TIME, BEHAVIORAL OSCILLATION The dichotomy of memory into working memory (short-term memory) and long-term memory has long been generally accepted. In particular, working memory has been assumed to consist of a single state to realize short-term memory retention. However, as we experience in everyday life, consciously focused memories can be retrieved more quickly than less focused memories, implying the existence of several states in working memory. Here, we hypothesized that working memory is not composed of a single state as conventionally believed, but instead consists of co-existing multiple states. In this study, we developed a new experimental paradigm to measure the reaction time required to recall an alphabet when presented with a corresponding color, based on the memorized five pairs of colors and alphabets. The results demonstrated that when the same color as the previous trial was presented (Same condition), the reaction time distribution was short and monophasic, indicating that only the most recent memory was easily accessible as an active state. On the other hand, when the different color from the previous trial was presented (Different condition), a slower polyphasic distribution was obtained. Surprisingly, the reaction time distribution in the Different condition showed rhythmicity in the theta-alpha band (3-10 Hz). This behavioral rhythmicity indicates that the time taken to recall non-recent memories was slow, discrete, and periodic, suggesting that non-recent memories were in a semi-active state and accessed by scanning in the theta-alpha rhythmic manner. These results point to the need to reconsider the conventional assumption that working memory is composed of a single state and suggest the co-existence of multiple states, namely, active and semi-active states. We further found that the capacity of the active state is extremely limited. This suggests that we can only be aware of a few bits of information at a time, and that multiple pieces of information coexist through rhythmic reactivation by neural oscillations. We further found that the capacity of the active state is extremely limited. This suggests that we can only be aware of a few bits of information at a time, and that multiple pieces of information coexist through rhythmic reactivation by neural oscillations.		2022年6月30日　13:00～14:00　沖縄コンベンションセンター展示棟　ポスター会場1 1LBA-076 リスク下の決定におけるヒトの脳の機能的連結 Functional connectivity of human brain in risk desicions 浅水屋剛(1)、武居寛史(2)、太田勝造(4,1)、國吉康夫(3)、加藤淳子(1) 1. 東京大学大学院法学政治学研究科、2. 東京都立大学法学政治学研究科、3. 東京大学大学院情報理工学系研究科、4. 明治大学法学部 Takeshi Asamizuya(1), Hirofumi Takesue(2), Shozo Ota(4,1), Yasuo Kuniyoshi(3), Junko Kato(1) 1. Grad Sch Law and Politics, The University Of Tokyo, 2. Grad Sch Law and Politics, Tokyo Metropolitan University, 3. Grad Sch Info Sci Tech, The University Of Tokyo, 4. School of Law, Meiji University Keyword: fMRI, DCM, prospect theory, risk desicions Humans make a decision under risk depending on subjective, rather than objective, evaluation of values. The existing MRI studies examined this prediction of prospect theory, and found the activation of emotion-related regions. However, the function connectivity associated with human risk decision is still unknown. This MRI experiment has adopted dynamic causal modelling (DCM) to conduct a model comparison using the parametric empirical Bayes (PEB) method, and explicated the functional connectivity of the brain associated with human behavioral tendency under risk. Inside MRI, subjects repeated to choose one out of two lotteries with the same expected values, but with distinct framing of gain and loss, respectively. Activation has been found in the right and left insula, precuneus, BA9/44, and BA32/8, when making risk decisions either with gain and loss framings. The functional connectivity of these activated regions was, however, dissociated by loss and gain framings, especially the one between the insula and the prefrontal cortex was. Neural results were also underlined by distinct behavioral tendencies, i.e., risk-aversion and risk-seeking when choices are framed as gains and losses, respectively. When we cross-examined the individual risk tendency based on repeated choices under different framings, the neural result also implied that subjective risk function was represented in the functional connectivity between the emotion-related regions (i.e., the right and left insulas) and the prefrontal cortex associated with cognitive control (i.e., BA 9/44 and BA32/8). Overall, a difference in human risk attitude is not detected by brain activation, but is associated with distinct connectivity of activated regions. This supports the importance of connectivity analysis to advance understanding of human social behavior.

2022年6月30日　13:00～14:00　沖縄コンベンションセンター展示棟　ポスター会場1 1LBA-077 経験効用のトレンドが決定効用を決める Trends in experienced utility determine decision utility 松森嘉織好(1,2,3)、飯島和樹(1,4)、佐伯百合子(5)、平林和恵(5)、互恵子(5)、松元健二(1) 1. 玉川大学、2. 東京大学、3. 日本学術振興会、4. 国立精神・神経医療研究センター、5. 資生堂 Kaosu Matsumori(1,2,3), Kazuki Iijima(1,4), Yuriko Saheki(5), Kazue Hirabayashi(5), Keiko Tagai(5), Kenji Matsumoto(1) 1. Tamagawa Univ, 2. Univ of Tokyo, 3. Japan Society for the Promotion of Sci, 4. Natl. Ctr. of Neurol. and Psychiatry, 5. Shiseido Co., Ltd Keyword: DECISION MAKING, REWARD, FMRI There has long been tension between two different usages of the term "utility". Decision utility, adopted in current economics and decision theory, refers to the weight of an outcome in a decision and is inferred from observed choice behavior. However, in classical utilitarianism, utility refers to pleasure and pain, and such experienced utility can be reported in real time (instant utility), or in retrospective evaluations of past episodes (remembered utility). To bridge these two core meanings of utility in the human brain, we developed a novel task for measuring neural correlates of decision, instant and remembered utility. By choosing between two fractal images, participants received a series of monetary rewards depending on the chosen image in 10 discrete steps repeated. Occasionally, participants were asked to report their current pleasantness (instant utility) or retrospective pleasantness (remembered utility) for the fractal image. We assigned six different patterns of reward series (descending (D), constant (C), and ascending (A) patterns of large rewards and those patterns of small rewards) to six fractal images, respectively. Participants gradually learned the value of fractals and showed rational choice behavior (large vs. small). Interestingly, even among the same reward category (large or small), they showed particular preference for reward series (i.e., D > C > A). The remembered utility for each reward series gradually dissociated from the others, reflecting the learning of value. Reported instant utility roughly reflected the trends of monetary reward series. However, the sums of instant utilities over the whole steps were dramatically dissociated from objective reward amounts. The instant utility of later steps seemed to be less affected by reward amounts. The sum of instant utilities over the whole steps also seems to reflect the preference for reward series in choice behavior. Moreover, a multiple regression analysis to instant utility indicated that presenting particular series itself affected instant utility regardless of current amounts of monetary reward. Furthermore, we developed computational models to examine the dependency among utilities and reward. Model selection confirmed that instant utility, in addition to the objective reward, had a role in determining remembered and decision utility. The selected model suggests that trends in instant utility determine decision utility through remembered utility. As the next step, we will analyze the neural responses with the newly developed decision-making model to differentiate the three utilities in the brain.		2022年6月30日　13:00～14:00　沖縄コンベンションセンター展示棟　ポスター会場1 1LBA-078 Drosophila subobscuraの脳内インスリン産生ニューロンは吻運動を制御して種特異的な求愛行動を生み出す Brain-insulin neurons modulate proboscis motor activity for generating species-specific courtship behavior in Drosophila subobscura 原佑介(1)、田中良弥(2)、古波津創(1)、佐藤耕世(1)、山元大輔(1) 1. 情報通信研究機構未来ICT研究所、2. 名古屋大学大学院理学研究科 Yusuke Hara(1), Ryoya Tanaka(2), Soh Kohatsu(1), Kosei Sato(1), Daisuke Yamamoto(1) 1. Adv ICT Res Inst, NICT, Hyogo, Japan, 2. Grad Sch Sci, Nagoya Univ, Aichi, Japan Keyword: Species-specific behavior, fruitless, insulin, neural circuit Nuptial gift is an obligatory male courtship ritual in Drosophila subobscura but not in other Drosophila species: a male gives mouth to mouth regurgitated crop contents to a mate. To elucidate how the behavioral specificity arises during evolution, we studied the neural circuitry for the nuptial gift giving. We focused on neurons that express sex-specific products of the fruitless (fru) gene FruM since FruM is known to instruct formation of the courtship neural circuit both in D. melanogaster and D. subobscura. We identified a few neurons that promote the nuptial gift giving, which include insulin-producing cells (IPCs) in the brain and motoneurons in the suboesophageal ganglion, putative IPC postsynaptic targets. We found that the motoneurons innervated proboscis muscle 9 (m9), which is involved in rostrum and haustellum movements in the proboscis. To ask whether IPCs would be associated with the regulation of m9 activity, we performed intracellular recording of membrane potential from m9 muscle fibers while simultaneously optogenetically activating IPCs. We found that m9 fibers showed spontaneous electrical activities that are characterized by repetitive volleys of depolarizing potentials when IPCs were not activated, suggesting that the central pattern generator underlies the m9 activity to control the proboscis motor program. Intriguingly, the optogenetic activation of IPCs immediately suppressed the occurrence of these repetitive volleys of depolarizing potentials in m9 in D. subobscura, but not in D. melanogaster. We postulate that IPCs modulate motor outputs to pharyngeal muscles, particularly m9, within the central circuit that controls regurgitation in D. subobscura but not D. melanogaster.

2022年6月30日　13:00～14:00　沖縄コンベンションセンター展示棟　ポスター会場1 1LBA-079 確証バイアス下におけるメタ認知プロセスに関わる神経基盤の分離 Neural Dissociation of Metacognitive Processes Under Confirmation Bias 南條啓孝(1,2,3)、Aguilar Lleyda David(3)、山本哲也(1,2)、赤石れい(3)、定藤規弘(1,2) 1. 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心理生理学研究部門、2. 国立大学法人総合研究大学院大学、3. 国立研究開発法人理化学研究所　理研CBS-トヨタ連携センター　　社会価値意思決定ユニット Yoshinori Nanjo(1,2,3), David Aguilar Lleyda(3), Tetsuya Yamamoto(1,2), Rei Akaishi(3), Norihiro Sadato(1,2) 1. Department of System Neuroscience, National Institute for Physiological Sciences, 2. The Graduate University for Advanced Studies, 3. Social Value Decision-Making Collaboration Unit, RIKEN Centre for Brain Science BTCC TOYOTA collaboration centre Keyword: CONFIRMATION BIAS, DECISION-MAKING, METACOGNITION, fMRI Subjective confidence in our decisions is believed to guide post decisions processes. Estimatingconfidence is an integral part of metacognition, which works to monitor and regulate our cognitive processes. Although this can help us improve our decisions, it does not always lead to optimal decisions. Once we commit to a decision with high confidence, this may bias us toward sticking with the initial decision,making us reluctant to incorporate new evidence (Rollwage et al., 2020). Such selective incorporation of information is called confirmation bias (Tversky and Kahneman, 1974) and numerous studies have been reported on this phenomenon in a variety of situations. However, little is known about the effects of spontaneously produced confidence on the post decision processes and its neural mechanisms.To examine these issues, we conducted an fMRI experiment in 34 subjects who performed a task of two sequential perceptual decision-making with confidence reports. Subjects were presented with two circular stimuli on the screen and required to indicate which of the two stimuli was larger and rate the confidence in their decision. To assess how initial confidence would influence post decision processes, all trials were median-split according to initial confidence level. We calculated the probability of changing mind (1st and 2nd decisions being different).We found that the subjects more likely repeat the initial decision at the second decision when they report more confidence at the first decision. Thus, the results revealed that our pre-existing confidence reduces cognitive flexibility. The next question is whether this behavioral interaction of metacognition and confirmation bias (change of mind) is subserved by the overlapping systems of metacognitive processes. The fMRI results revealed that, at the timing of initial decision, significantly higher activity in the medial part of the frontal pole area when the subjects report higherconfidence. We also found higher activation in left anterior cingulate cortex at the same timing if a change of mind occurred at the second decision. The fMRI result shows that no brain area was commonly activated by each metacognitive process.Because these areas are considered as separate neuralsystems based on the anatomical connectivity patterns (Passingham et al., 2002, Neurbert et al. 2015), metacognitive processes under confirmation bias are neurally dissociable.		2022年6月30日　13:00～14:00　沖縄コンベンションセンター展示棟　ポスター会場1 1LBA-080 知覚意思決定時におけるマウス聴覚皮質での証拠強度と報酬バイアスの表現 Representation of evidence strength and reward bias in mouse auditory cortex during perceptual decision making 石津光太郎(1)、西本翔裕(1)、船水章大(1) 1. 東京大学定量生命科学研究所 Kotaro Ishizu(1), Shousuke Nishimoto(1), Akihiro Funamizu(1) 1. Institute for quantitative biosciences, Univ of Tokyo, Tokyo, Japan Keyword: Perceptual decision making, Neuronal representation, Reward bias, Sensory evidence When making decisions, subjects choose the option with high expected reward or high action value. In a two-alternative forced choice task, recent study shows that the action value is estimated not only from the amount of reward (prior knowledge) but also from the certainty of sensory cues. This study investigates how the integration of prior knowledge and sensory inputs is carried out in the brain. Six wild-type CBA/J mice were subjected to a tone-frequency discrimination task in which a high- or low-frequency tone was associated to a left- or right-spout water reward. The task changed the amount of rewards in every 90 to 120 trials (block) and presented either a long- or short-tone in each trial. Consistent with our previous study (Funamizu, iScience, 2021), mice changed their choices based on both the reward amounts and tone durations: the choices were less accurate and more biased by the asymmetric reward block in short- than in long-stimulus trials. During the task, we electrophysiologically recorded the neuronal activity of auditory cortex with Neuropixels 1.0. Analyses of single-unit activities showed that the auditory cortical neurons changed the firing rates by the stimuli evidence, indicating their sound encoding. Some neurons also changed the activity by the asymmetric reward blocks. Because the reward modulation of activity was observed both in the positive and negative directions in terms of the preferred sound tuning, the population sound encoding became stable across blocks. So far, our results suggest that the auditory cortex plays a role in representing sensory cues and transmitting them to upstream areas; the integration of prior knowledge and sensory inputs are performed in outside of the auditory cortex. We are currently recording the activity of medial prefrontal cortex and the secondary motor cortex to investigate whether these two areas integrate the prior knowledge of reward and sound inputs.

2022年6月30日　13:00～14:00　沖縄コンベンションセンター展示棟　ポスター会場1 1LBA-081 将棋における意見の不一致と受容に関する脳波反応 Electrophysiological responses to disagreement and acceptance in shogi 志水信哉(1)、太田藍李(1)、戸嶋巌樹(1)、小澤史朗(1) 1. 日本電信電話株式会社人間情報研究所 Shinya Shimizu(1), Airi Ota(1), Iwaki Toshima(1), Shiro Ozawa(1) 1. NTT Human Informatics Laboratories, NTT Corporation, Tokyo, Japan Keyword: Event-Related Potential (ERP), Shogi (Japanese Chess), Communication One of the major roles of communication is to coordinate opinions with others. Especially in order to utilize a diverse of values and ideas, it is very important to understand whether one's opinion is aligned with that of the other person and whether the other person accepts one's opinion. In this study, we investigate electroencephalographic (EEG) responses to alignment/misalignment and acceptance/rejection. Existing studies have shown that misalignment with assumptions arising from context and knowledge induces the N400 event-related potential (ERP) response. Furthermore, it has also been reported that the N600 was induced by the process of trying to resolve such contradictions through logical thinking. However, the discrepancies in these studies are obvious and rarely happened in natural dialogues. However, the discrepancies in these studies are obvious and rarely happened in natural dialogues. Therefore, in this study, we used the discussion of the next move in Shogi as the situation where natural conflicts of opinion occur. We obtained subjective evaluation on the suggestion of the next move for the given situation in terms of alignment with your opinion and acceptance of the suggestion, EEG data were also recorded for the ERP analysis. The experiment was conducted on advanced Shogi players, and suggestion on the next move against a position with victory paths was presented on the screen in text. We prepared three types of next move suggestions: the best move, a move that is not the best but leaves a victory path and a move that eliminates the critical clue. ERP analysis was performed targeting the timing of presentation of the phrase that indicated that the move was different from the best move. The results of the ERP analysis showed that negative potentials tended to occur around 350-450ms and 600-700ms when the participants answered "not consistent with my opinion" or "not acceptable". Comparing the EEG responses between "inconsistent with my opinion but accepting" and "inconsistent with my opinion and rejecting", it was confirmed that the occurrence of negative potentials at both timings was smaller in the former case. These results indicate that N400 component, which relates to detection of the unanticipated information, occurs even in cases of disagreement with one's own suggestion without apparent semantical or grammatical contradiction, but that this response may be influenced by whether or not one can ultimately agree with the suggestion.		2022年6月30日　13:00～14:00　沖縄コンベンションセンター展示棟　ポスター会場1 1LBA-082 短文指示に対する主観的印象のERP分析 An ERP analysis of subjective impression toward short-text instructions 太田藍李(1)、志水信哉(1)、戸嶋巌樹(1)、小澤史朗(1) 1. 日本電信電話株式会社人間情報研究所 Airi Ota(1), Sinya Shimizu(1), Iwaki Toshima(1), Shiro Ozawa(1) 1. NTT Human Informatics Laboratories, NTT Corporation, Tokyo, Japan Keyword: Event-related potentials (ERPs), N400, P600, Subjective impression In the field of education and training, it is important to correctly understand the receiver's impression and other reactions to instruction in order to provide appropriate instruction. We are, therefore, investigating a method to recognize the receiver’s impression from electroencephalography (EEG). Existing studies have shown that event-related potential (ERP) components such as N400 and P600 occur in response to anomalies in sentences. The N400 is sensitive to a variety of semantic factors, including world knowledge violations and semantically anomalous words. The P600 response has been observed to occur in response to syntactic anomalies and syntactically unexpected words, as well as syntactically complex sentences. However, the "world knowledge violations" and "syntactic anomalies" addressed in these studies are rarely happened in our daily lives. In addition, these existing studies have only investigated objective responses that are clearly and/or commonly unnatural, and have not targeted subjective impressions toward the presented sentences. In this study, we obtained the receivers' objective and subjective impressions of anomaly, convinced, and acceptance for the natural short-text instruction, and EEG data were also recorded for the ERP analysis. In the experiment, short-text instructions were presented for participants with dividing by a few phrases words. The instructions can be classified into three categories: natural, semantically unnatural, and controversial i.e., subjective impressions differ depending on the individual. The three categories consisted of 30 questions each. ERP analysis was conducted targeting the timing of the presentation of phrases that determined the presence or absence of anomalies. The results showed that some significant N400 and P600 components were observed for instructions that the participants reported as anomalous or unacceptable. Comparing the differences in EEG response between presence and absence of anomalies with those between acceptance and rejection, we found the larger P600 response in the presence of anomalies, and the larger N400 response in rejection. In relation to the sense of conviction, the N400 component was observed when unconvincing, but no significant P600 was identified. These results indicate that the amplitudes of N400 and P600 can be one of the cues for recognizing subjective as well as objective impressions.

2022年6月30日　13:00～14:00　沖縄コンベンションセンター展示棟　ポスター会場1 1LBA-083 扁桃体領域による社会的接触行動の制御機構 Amygdala-dependent neural circuit mechanisms of social contact behavior 福光甘斎(1)、黒田公美(1) 1. 理化学研究所脳神経科学研究センター Kansai Fukumitsu(1), Kumi O Kuroda(1) 1. RIKEN Center for Brain Science Keyword: Social behavior, Amygdala, Calcitonin receptor Social animals proactively engage in affiliative contacts among conspecifics, and exhibit stress responses upon isolation. The neural mechanisms required for sensing and seeking for social contacts have yet to be elucidated. In our recent publication, we have reported that isolation of female mice from free social interaction via partition window induces contact-seeking behavior and social reunion following 2 days of social isolation induces social contact behaviors such as peer-sniffing, allogrooming and crawling under peers. The amylin-calcitonin receptor signaling in the medial preoptic area (MPOA) mediates such affiliative social behaviors under acute social isolation or social reunion. We have also reported that central amygdala neurons, particularly in its medial part (CeM) were activated by social isolation, and that calcitonin receptor-expressing neurons in the medial amygdala posterodorsal part (MePD) were activated by social reunion. However, amygdala-dependent neural circuit mechanisms of affiliative social behavior have yet to be studied. Here we found that chemogenetic activation of CaMKIIa-expressing neurons in the CeM amplifies contact-seeking behavior during social isolation. On the other hand, targeted knockdown of CALCR gene in the MePD does not affect contact-seeking behavior during social isolation but amplifies social contact behavior during social reunion. These data suggest that different amygdala subregions mediate specific types of social contact behaviors under different social conditions.		2022年6月30日　13:00～14:00　沖縄コンベンションセンター展示棟　ポスター会場1 1LBA-084 インテリボード：新規社会行動評価系の開発および自閉症モデルマウスへの展開 IntelliBoard system: Development of a novel social behavior evaluation system and its application to Autism Spectrum Disorder model mouse 越智翔平(1)、上甲なつみ(1)、稲田仁(1,2)、大隅典子(1) 1. 東北大学大学院医学系研究科、2. 東北大学大学院医工学研究科 Shohei Ochi(1), Natsumi Joko(1), Hitoshi Inada(1,2), Noriko Osumi(1) 1. Tohoku University Graduate School of Medicine, 2. Tohoku University Graduate School of Biomedical Engineering Keyword: Social behavior test, Multiple mouse analyses, ASD/ADHD model, Pax6Sey/+ mouse Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder (ND) characterized by social communication deficits and repetitive behaviors. Recently, the number of children diagnosed with ASD or related attention-deficit/hyperactivity disorder (ADHD) has been increasing. Therefore, further elucidation of the pathogenic mechanisms and symptoms of ND would be a critical issue. Animal models for ND have been currently explored by classical behavioral paradigms such as the open field test and the social interaction test. However, it is challenging to reproduce situations corresponding to neuropsychiatric symptoms, such as anxiety and hypertension in social environments, which are considered problems in human ND. To address this task, we developed a novel behavior analysis system (IntelliBoard) in combination with IntelliCage. This system allows us to analyze the relative distances between individual mice and the travel distances of multiple mice without image analysis by embedding a transponder in individual mice. The relative distance between two individuals obtained from the IntelliBoard could be an affinity indicator with others and anxiety in the social environment. Preliminary analysis using wild-type (WT) and autism model (Pax6 heterozygous mutant; Pax6^Sey/+) mouse littermates showed pronounced differences in social behavior between these two genotypes. In our previous study (Yoshizaki et al., 2016), an open-field test for 20-minutes showed no significant differences in the anxiety behavior of WT and Pax6^Sey/+ mice under similar growing conditions as in the present study. The open-field test for longer-term by the other laboratory has reported that another Pax6 mutant strain (Pax6^Leca2) showed a larger travel distance than the WT strain during the light period (Chhabra et al., 2020), consistent with our results. Based on our and previous studies, Pax6^Sey/+ mice possibly feature hyperactive behavior and are a potentially helpful model for ASD with concomitant ADHD. IntelliBoard would be a valuable system for studying neuropsychiatric behaviors in ND model mice. Our system might provide an alternative method to classical behavioral analysis because it allows 1) a long-term study without image analyses, 2) quantitative analyses of anxiety in social environments, and 3) exploration of behavioral phenotypes that are difficult to detect in conventional short-term open field tests.

2022年6月30日　13:00～14:00　沖縄コンベンションセンター展示棟　ポスター会場1 1LBA-085 性周期は雌マウスの社会的ヒエラルキーの変動性を引き起す Sexual Cycles Trigger Variability in the Social Hierarchy of Female Mice 北村和音(1)、濱崎友美(1)、南雅文(1)、天野大樹(1) 1. 北海道大学 Kitamura Kazune(1), Yumi Hamasaki(1), Masabumi Minami(1), Taiju Amano(1) 1. Hokkaido University Keyword: social hierarchy, female mice, tube test Social hierarchy is the fundamental organizing mechanism of animal societies, arising in relation to competition for resources such as food, mates, and physical space. It is known that in male mice, social hierarchy with low variability is formed to minimize intense fights among group members, and many studies have revealed the related mechanisms in the brain. On the other hand, social hierarchy in female mice, whose behavioral patterns are unstable because of their sexual cycle, has not been well studied. In this study, we examined social hierarchies in groups of male and female C57BL/6J mice, each consisting of four animals, using the tube test to compare differences between the sexes. Ranks were assigned based on the number of wins in each day's tube test, and the absolute value of the difference from the previous day's rank in each mouse was taken to compare the variability in rank between male and female mice. The results showed that the ranks of social hierarchy varied significantly more in female mice than in male mice on each experimental day. Therefore, to determine the effect of the sexual cycle on the ranks of female mice, we performed the tube test using ovariectomized (OVX) mice. As a result, we found that the rate of fluctuation in ranks was decreased by ovariectomy. Open field tests in OVX females showed no significant differences in locomotor activity or time spent in center zone between the first- and fourth-ranked mice. The results suggest that fluctuations in social hierarchy in female mice are influenced by the sexual cycle. Future studies will address the effects of sex hormones on female social hierarchy and the mechanisms in the brains of female mice to develop social hierarchy.		2022年6月30日　13:00～14:00　沖縄コンベンションセンター展示棟　ポスター会場1 1LBA-086 課題の報酬額の予告に対する腹側線条体の活動が後続の寄付行動に関連する Activation of ventral striatum for pre-trial notice of reward amount of task relates to subsequent donation behavior 小川昭利(1,4)、黒田起吏(2,3)、亀田達也(2,4,5) 1. 順天堂大学医学部、2. 東京大学大学院人文社会系研究科、3. 日本学術振興会、4. 玉川大学脳科学研究所、5. 北海道大学社会科学実験研究センター Akitoshi Ogawa(1,4), Kiri Kuroda(2,3), Tatsuya Kameda(2,4,5) 1. Faculty of Medicine, Juntendo Univ, Tokyo, Japan, 2. Grad Sch Humanities and Sociology, Univ of Tokyo, Tokyo, Japan, 3. Japan Society for Promotion of Science, Tokyo, Japan, 4. Brain Science Institute, Tamagawa Univ, Tokyo, Japan, 5. Center for Experimental Research in Social Sciences, Hokkaido Univ, Sapporo, Japan Keyword: FUNCTIONAL MAGNETIC RESONANCE IMAGING, REWARD, SOCIAL COGNITION, DECISION-MAKING Donation to unrelated people through a social welfare organization is an outstanding sociality of humans. However, the cognitive and neural bases for determinants of donation behavior have not been fully understood. In this functional magnetic resonance imaging experiment, we investigated how a brain region in the reward system mediated the donation behavior. The participants were asked to perform a calculation task and donate any rate from their own reward of the task. The difficulties of calculation and the reward amounts were factorially designed. The participants were instructed that their donations were sent to a social welfare organization. The behavioral results showed that the reward amount appearing in the notice cue was strongly related to the subsequent donation rate, although the difficulty did not influence the donation rate. The imaging result showed that the ventral striatum, a region in the reward system, was associated with the reward amounts in the notice cue. The results of mediation analysis showed that the ventral striatum partly and negatively mediated the donation rate. In contrast, the donation behavior was unrelated to the brain regions associated with theory-of-mind that were identified by a functional localizer. These results suggest that the reward system may influence charitable behaviors independently from cognitive perspective taking as associated with theory-of-mind.

2022年6月30日　13:00～14:00　沖縄コンベンションセンター展示棟　ポスター会場1 1LBA-087 島皮質を介した社会行動制御の神経機構 Neural mechanisms of social behavior in the insular cortex 藤間秀平(1)、佐藤正晃(2)、中井信裕(1)、内匠透(1) 1. 神戸大学大学院医学研究科、2. 北海道大学大学院医学院 Shuhei Fujima(1), Masaaki Sato(2), Nobuhiro Nakai(1), Toru Takumi(1) 1. Kobe University School of Medicine, Kobe, Japan, 2. Hokkaido University School of Medicine, Sapporo, Japan Keyword: Social behavior, Autism, Neural circuit Social interaction and communication behaviors are critical for social animals, including humans. Although there are significant individual differences in social behaviors, reduced sociability is one of the features of psychiatric disorders such as autism spectrum disorders (ASDs). However, the detail of the neural mechanism underlying social behavior remains unclear. Recently, it has been reported that injuring the insular cortex (IC) causes social behavior impairments, and the decreased neural activity of IC is found in individuals with ASDs, suggesting that IC is one of the important brain regions for social behavior. Our laboratory previously reported that information on social interaction behavior was encoded in the neural ensembles named “Social Cells” that exist in IC neurons of mice [Miura et al., 2020]. Since the previous study investigated the Social Cells in the population of CaMKII-positive pyramidal neurons, there remain questions 1) whether other cell types of IC neurons are categorized as Social Cells and 2) whether the IC Social Cells functionally regulate social behavior. To address these questions, we conducted experiments of cell type-specific neural recording and optogenetic manipulation of IC neurons in mice during social behavior. First, we examined parvalbumin (PV)-positive interneurons by in vivo calcium imaging. We injected the AAV-syn-flex-GCaMP6f viral vector into the IC of PV-cre transgenic mice and recorded cellular activities of the PV interneurons by microendoscopic calcium imaging during social interaction with unfamiliar conspecifics in the home cage. As a result, 11% of PV interneurons were activated and 17% were suppressed during the social interaction, suggesting that the neural ensembles of PV interneurons encode social interaction behavior. Next, we injected AAV5-CaMKII-Jaws into IC to optogenetically suppress the neural activity of IC neurons during social behavior. The social interaction ratio was decreased by optogenetic suppression, suggesting that neural activity of CaMKII-positive IC neurons is necessary to express pro-social behavior. Taken together, our study indicates that both subpopulations of IC pyramidal neurons and interneurons encode social information and may modulate social behavior by mutual control among excitatory and inhibitory circuits.		2022年6月30日　13:00～14:00　沖縄コンベンションセンター展示棟　ポスター会場1 1LBA-088 小脳グリア活動による攻撃行動制御機構 The role of cerebellar glial activity in aggressive behavior 淺野雄輝(1)、松井広(1) 1. 東北大学生命科学研究科 Yuki Asano(1), Ko Matsui(1) 1. Graduate School of Life Sciences, Tohoku University, Sendai, Japan Keyword: Cerebellum, Aggression, Neuron-glial interaction, Fiber photometry The cerebellum has a key role in motor learning. However, the cerebellum has also been shown to be strongly associated with social cognition. Synaptic connection from the deep cerebellar nuclei (DCN) to the ventral tegmental area has recently been discovered. As the sole output from the cerebellum is carried by the axons of Purkinje cells (PCs), and, as PCs are GABAergic inhibitory neurons, the heightened activity of PCs leads to inhibition of the DCN activity. Therefore, increase and decrease in PC activity have been shown to lead to reduction and enhancement of aggressive behavior, respectively. Using glial optogenetics, we have previously shown that cerebellar Bergmann glial cell (BG) has strong control over the activity of PCs. Therefore, we hypothesized that BG activity has a pivotal role in regulating social cognition and aggressive behavior. A FRET Ca2+ sensor YCnano was specifically expressed in astrocytes including cerebellar BGs. An optical fiber was implanted into the vermis of the cerebellum and fiber photometry was conducted in freely moving male mice. After habituation of the optical fiber implanted mouse in a novel cage environment, an intruder male mouse was placed in the recording chamber. Depending on the combination of mice with different individual character, aggressive behavior was sometimes induced. Fluorescent signals from the cerebellum were strongly affected by the aggressive behavior and the social proximity of the two mice. The signals changed with both the attack initiated by the resident mouse or with the attack from the intruder mice. The difference in the signal accompanied by aggressive and defensive behavior is currently being analyzed. Interestingly, FRET was not always apparent and, in many cases, the fluorescence of all wavelengths decreased with these aggressive social encounters; thus, we hypothesized that local brain blood volume was increased. Social stimuli derived neuronal signal input to the cerebellum could induce adenosine release from the BGs. Adenosine may act on the blood vessels to increase the vascular volume, while the same adenosine could suppress the firing of PCs, which could lead to the disinhibition of the DCN and to the increased aggressive behavior. Based on this hypothesis, we are currently evaluating the role of neuron-glia-vascular interaction in the regulation of aggression and social behavior.

2022年6月30日　13:00～14:00　沖縄コンベンションセンター展示棟　ポスター会場1 1LBA-089 発情は雌マウスの社会的優位性を高める Estrus raise social dominance among female mice 山﨑夏子(1)、北村和音(1)、濱崎友美(1)、南雅文(1)、天野大樹(1) 1. 北海道大学 Natsuko Yamazaki(1), Kazune Kitamura(1), Yumi Hamasaki(1), Masabumi Minami(1), Taiju Amano(1) 1. Hokkaido University Keyword: social hierarchy, hormone, female mice, electrophysiology Social hierarchy arises in relation to the successes in survival, health, and reproduction and is one of the basic principles for organization of animal societies. Using a tube test, we have shown that social dominance among female mice may be influenced by the sexual cycle. We also found that the ranks in the tube test were more stable among female mice whose sexual cycle was stopped by ovariectomy (OVX). In this study, we aimed to address the relationship between sexual hormones and social dominance. When estradiol and progesterone were administered intraperitoneally to the lowest-ranked OVX-treated mice, their ranks in the tube test were raised. On the other hand, estradiol alone (without progesterone) did not raise the rank significantly. These results suggest that estrus in female mice raised the rank in the tube test. Next, we tried to address the effects of estrus on the neuronal circuits in the brain with focusing on the medial prefrontal cortex (mPFC), the brain region in which glutamatergic synaptic transmission has been reported to be potentiated in the higher ranked mice. Whole-cell patch-clamp recordings was performed to examine the effect of sexual hormones on the glutamatergic transmission in the mPFC. However, the results showed that the amplitude and frequency of mEPSC did not change in the vehicle, estradiol, and estradiol plus progesterone groups. We will discuss the neural mechanisms how hormones and behavioral experiences contribute to the formation of social dominance.		2022年6月30日　13:00～14:00　沖縄コンベンションセンター展示棟　ポスター会場1 1LBA-090 家族飼育のマーモセットにおける新しい3次元トラッキングシステムの開発 Development of a new 3D tracking system in family-reared marmosets. 圦本晃海(1)、井上貴史(1)、菊池理加(1)、渋木裕介(1)、早瀬川由美(1)、上岡美智子(1)、橋本りの(1)、山崎栄子(1)、佐藤賢哉(1)、汲田和歌子(1)、佐々木えりか(1) 1. 公益財団法人　実験動物中央研究所 Terumi Yurimoto(1), Takashi Inoue(1), Rika Kikuchi(1), Yusuke Shibuki(1), Yumi Hayasegawa(1), Michiko Kamioka(1), Rino Hashimoto(1), Eiko Yamazaki(1), Kenya Sato(1), Wakako Kumita(1), Erika Sasaki(1) 1. Central Institute for Experimental Animals Keyword: marmoset, behavior, 3D tracking Many of behavioral abnormalities are caused by symptoms of many neurological disorders. The common marmosets (Callithrix jacchus) social behaviors are similar to those of humans than rodents, such as family-based herding and food-sharing behaviors. Recently, various genetically manipulated marmoset models of neurodegenerative diseases have been created. However, it is unclear when and how the new genetically modified marmoset models will develop symptoms. Therefore, an automated behavioral analysis system that accurately detects and quantifies the lifelong behaviors of the model animals is necessary. However, there are no reports of behavior analyzers for large cages that can accommodate multiple marmosets or marmoset families. This study developed a novel behavior analysis system that combines light detection and ranging (LiDAR), video tracking, and deep learning for automatically tracking and analyzing individual behaviors of multiple marmosets in a family cage were tracked and their behaviors detected. A family of three marmosets were kept in a family cage (W820 × D610 × H1578 mm) in accordance with EU guidelines. At the front and back of the cage were installed acrylic panels for acquisition of images from cameras and LiDAR. Four LiDAR and four cameras were set up in front of the cage. LiDAR and video tracking by deep learning were used to detect the positions of individual marmosets and create trajectories for each scene. In addition, the animal behaviors were detected by deep learning of video frames to determine their content and location. So far, the face recognition accuracy is more than 98%. Their trajectories were tracked independently by combining video, 3D coordinates detected by light detection and ranging (lidar) systems, and facial identification. Location preferences and distances between individuals were calculated using the 3D trajectories and grooming behavior was detected by deep learning (recall: 79.1%, precision: 90.5%). This novel system will allow the quantification of individual captive animals within groups, facilitating the quick and automatic measurement of social behavior, and enhancing development of objective behavioral indices.

2022年6月30日　13:00～14:00　沖縄コンベンションセンター展示棟　ポスター会場1 1LBA-091 Dopaminergic modulation of mental state attribution Schuster Bianca(1,2,5)、Sowden Sophie(2,5)、Rybicki Alicia(2,5)、Fraser Dagmar (5)、Press Clare(3,6)、Holland Peter(4)、Cook Jennifer(2,5) Bianca Annkathrin Schuster(1,2,5), Sophie Sowden(2,5), Alicia J. Rybicki(2,5), Dagmar Scott Fraser(5), Clare Press(3,6), Peter Holland(4), Jennifer Louise Cook(2,5) 1. Institute of Advanced Sciences, Waseda University, Japan, 2. School of Psychology, University of Birmingham, UK, 3. 2Department of Psychological Sciences, Birkbeck University of London, UK, 4. Department of Psychology, Goldsmiths University of London, UK, 5. Centre for Human Brain Health, Birmingham, UK , 6. Wellcome Centre for Human Neuroimaging, UCL, UK Keyword: dopamine, social cognition, Theory of mind, executive function The ability to accurately attribute mental states (e.g., beliefs or desires) to others and oneself is integral to successful everyday social interaction (also referred to as mentalizing or Theory of Mind [ToM]). So called animations tasks, which require participants to attribute mental states to two interacting triangles, have consistently revealed atypicalities in a range of clinical populations. Intriguingly, among the clinical groups which show performance differences to controls in these tasks, dopamine dysfunctions are highly prevalent (e.g., Parkinson’s disease, Huntington’s disease or schizophrenia), suggesting a causal implication for dopaminergic signaling in ToM. However, currently there is no experimental evidence directly linking dopamine system dysfunction to atypical social cognition. Using our own established version of the animations task, the current study aimed to investigate whether disruption of the dopamine system causally affects mental state attribution. In a double-blind, placebo-controlled within-subject design, 33 participants (16 males; mean age = 26.36) received 2.5mg of the dopamine D2 receptor antagonist haloperidol on one, and a placebo tablet on another day, before viewing and labelling animations of triangles displaying mental state and non-mental state interactions. To control for interindividual variance in drug responsivity, participants’ performance in a visual working memory task was used as a proxy for individual baseline dopamine function (WM span has been shown to be a reliable indicator for striatal dopamine synthesis capacity). Using Bayesian mixed effects models, we observed that haloperidol resulted in decreased accuracy in labelling animations. Furthermore, adding WM span as a covariate revealed an interaction between drug and WM span, where individuals with low WM span (and hypothesized low striatal dopamine synthesis capacity) showed a stronger decrease in accuracy (Eμ_lowWM = -0.45, CrI = [-0.90, -0.14]) than participants with high WM span (Eμ_highWM = -0.19, CrI = [-0.43, 0.05]). Our results show direct effects of dopamine perturbation on performance in a widely used task of social cognition. Furthermore, the observed dependency of drug effects on individual baseline dopamine function is in line with previous cognitive studies and indicates that dopamine may modulate social cognition in a domain-general fashion, potentially by modulating prefrontal activity.		2022年6月30日　13:00～14:00　沖縄コンベンションセンター展示棟　ポスター会場1 1LBA-092 加齢に伴う脳機能障害とその生物学的基盤の探索 Analysis of age-related behavioral changes and their biological basis. 山田留衣(1)、永井裕崇(1)、沼知里(1)、堀川伊和(1)、永井碧(1)、川島祐介(2)、古屋敷智之(1) 1. 神戸大学大学院医学研究科、2. かずさDNA研究所 Rui Yamada(1), Hirotaka Nagai(1), Chisato Numa(1), Io Horikawa(1), Midori Nagai(1), Yusuke Kawashima(2), Tomoyuki Furuyashiki(1) 1. Graduate School of Medicine, Kobe University, 2. Kazusa DNA Research Institute Keyword: cognitive aging, aging, synaptic proteome Age-related dysfunction occurs in multiple cognitive domains. Aging causes declines in cognitive function and motivation, the biological basis of which remains unclear. We compared behavioral performance in two mouse strains, C57BL/6J (B6J) and C57BL/6N (B6N), to test for genetic variation.　In this study, we analyzed individual differences in cognitive aging using two behavioral tasks in different cognitive domains.　Mice first learned a visual discrimination task in which they were rewarded with food by responding to the correct of two visual stimuli. After learning of the visual discrimination task was established, the regularity of correct responses was switched. They then learned a response direction task in which food rewards were obtained by responding to either the left or right side of the stimulus. Attentional set shifting, which is behavioral flexibility between tasks, is known to be dependent on working memory. Aged B6N mice showed reduced motivation in both tasks. In contrast, the aged B6J mice maintained motivation for the task, but showed deficits in attentional set-shifting in some mice. Younger mice performed the visual discrimination and direction discrimination tasks without problems in both strains. In other words, individual differences in cognitive flexibility existed in old B6J mice. We also analyzed the synaptic proteome of the medial prefrontal cortex, a brain region important for attentional set-shifting. Young and old B6J mice showed differential expression of a number of synaptic proteins, some of which were increased only in a subset of old mice with unimpaired attentional set-shifting. These proteins were also highly expressed in younger individuals. These results suggest that there are distinct biological mechanisms, both genetic and synapse-related, that contribute to age-related declines in motivation and cognitive function.

2022年6月30日　13:00～14:00　沖縄コンベンションセンター展示棟　ポスター会場1 1LBA-093 環境エンリッチメントが脳発達に与える影響 Growing good enclosure may stimulate brain maturation 関布美子(1)、冨樫充良(1)、村岡俊典(1)、石淵智子(1)、黒滝陽子(1)、井上貴史(1)、圦本晃海(1)、向笠圭亮(1)、小牧裕司(1)、山田知歩子(1)、力武聖月(2)、伊東莉那(2)、佐々木えりか(1) 1. 実験動物中央研究所、2. 東京都立大学大学院　人間健康科学研究科 Fumiko Yurimoto Seki(1), Akiyoshi Togashi(1), Toshinori Muraoka(1), Tomoko Ishibuchi(1), Yoko Kurotaki(1), Takashi Inoue(1), Terumi Yurimoto(1), Keisuke Mukasa(1), Yuji Komaki(1), Chihoko Yamada(1), Mitsuki Rikitake(2), Rina Ito(2), Erika Sasaki(1) 1. Central Institute for Experimental Animals, 2. Tokyo Metropolitan University Graduate school of health sciences Keyword: brain development, environment, marmoset, MRI A large body of evidence has demonstrated the enriched environment has the considerable influence on the brain structure such as increasing brain weight and cortical thickness. In addition to studies with rodents, its influence on non-human primates needed to be studied to generalize findings further. To address it, using new world monkey common marmosets (marmosets), this study aimed to examine how the enriched environment was influenced on brain development. By longitudinal MRI measurement from young childhood until adulthood, we investigated which regions could be influenced by enriched environment in which stage of the development. Marmosets born and reared in enriched environment housing with their family members were regarded as enriched marmosets (N = 6, first/oldest twins, third twins, forth twins among 15 marmosets including parents). The room size was W 5240 x D 3560 x H2500 mm, which was large enough to observe natural locomotory behavior. Control marmosets (N = 6) were lived in the standard cage (W 410 x D 610 x H 730 mm). Marmosets were scanned from the age of 3 months until 18 months per 3 months with 7T MRI. T1 weighted image (T1WI) were utilized to analyze the brain morphology. Voxel-based morphometry (VBM) was conducted to examine longitudinal difference between enriched environment and standard cage. For the regions which were likely to change by VBM, we performed post hoc ROI analysis. VBM of the marmosets between enriched marmosets and controls at the age of 3-6-9 months showed the significant volume decrease in primary visual cortex. At the age of 12-15-18 months, the regions where the volume decreased significantly in enriched marmosets were shifted to second and third visual cortex, middle temporal area, auditory cortex, and premotor cortex. Post-hoc ROI analysis detected the volume of third/forth twins was more significantly decreased than that of first twins at the age 15 months. We found the decrease of brain volume occurred during brain development were likely to promote in certain regions when marmosets reared in enriched environment. It indicates their experience in enriched environment might promote the typical events occurred in development such as pruning of synapse. Most of these regions were in occipital lobe and temporal lobe which was associated with visual processing. It could be due to effects of spatial enrichment. Further, regions significantly decreased in later developmental stage were related to face perception as well, which was possible effect of social enrichment. Face perception was especially important for primates as they rely on face information for social interaction. Since family members increased as offspring were born in enriched enclosure, younger twins would possibly have more chances of social interaction than the oldest twins, which may lead to significant volume decrease and accelerate development.		2022年6月30日　13:00～14:00　沖縄コンベンションセンター展示棟　ポスター会場1 1LBA-094 血中ヘモグロビンは鋤鼻系により受容され化学感覚シグナルとして機能する Hemoglobin in the blood acts as a chemosensory signal via the mouse vomeronasal system 板倉拓海(1,2)、小坂田拓哉(1,2)、阿部峻之(1,2)、森裕美(1,2)、石井健太郎(1,2,5)、江口諒(1,2)、村田健(1,2)、齊藤航介(1,2)、𡌶-山中紗智子(1)、木本裕子(1)、吉原良浩(2,3)、宮道和成(1,2)、東原和成(1,2,4) 1. 東京大学大学院農学生命科学研究科、2. ERATO東原化学感覚シグナルプロジェクト、3. 理化学研究所脳神経科学研究センター、4. 東京大学ニューロインテリジェンス国際研究機構 Takumi Itakura(1,2), Takuya Osakada(1,2), Takayuki Abe(1,2), Hiromi Mori(1,2), Kentaro K Ishii(1,2,5), Ryo Eguchi(1,2), Ken Murata(1,2), Kosuke Saito(1,2), Sachiko Haga-Yamanaka(1), Hiroko Kimoto(1), Yoshihiro Yoshihara(2,3), Kazunari Miyamichi(1,2), Kazushige Touhara(1,2,4) 5. Present address, Univ of Washington, Center of Excellence in Neurobiology of Addiction, Pain, and Emotion (NAPE), Washington, USA Keyword: Vomeronasal system, Hypothalamus The vomeronasal system detects various environmental chemical cues and mediates appropriate behavioral responses depending on the animal's state. Here, we serendipitously found that blood activated the vomeronasal system in mice. We purified and identified the responsible compound in the blood as hemoglobin. Hemoglobin is detected by a specific vomeronasal receptor, Vmn2r88. By comparing bioactivity and amino acid sequence of hemoglobin from various animal species, we identified a crucial interaction site between hemoglobin and receptor. The hemoglobin signal reaches the accessory olfactory bulb and medial amygdala in male, virgin female, and lactating female mice. However, it activates the dorsal part of the ventromedial hypothalamus (VMHd), especially SF1-expressing neurons, in only lactating female mice. Exposure of hemoglobin to lactating female mice enhances digging and rearing behavior, a type of exploratory/risk assessment behavior, without affecting anxiety-related behaviors. The hemoglobin-mediated behavioral changes are lost in the receptor knockout mice. Finally, chemogenetic inhibition of SF1-expressing neurons in the VMHd disrupts hemoglobin-mediated digging enhancement, whereas optogenetic activation of these neurons with weak light intensity recaptures digging behavior in lactating female mice. Taken together, our results uncover the unidentified function of hemoglobin as a chemosensory signal and neural underpinnings behind the hemoglobin-mediated behavioral change in mice.

2022年6月30日　13:00～14:00　沖縄コンベンションセンター展示棟　ポスター会場1 1LBA-095 一人称条件下での状態・状況の知覚認知に関わる脳内情報表現 Representation of state and environment in the human brain under naturalistic first-person conditions 深井勇汰(1)、高木勇(1)、西本伸志(1,2) 1. 大阪大学　大学院生命機能研究科、2. 情報通信研究機構　未来ICT研究所脳情報通信融合研究センター Yuta Fukai(1), Yu Takagi(1), Shinji Nishimoto(1,2) 1. Osaka University Keyword: fMRI, Whole-brain voxel-wise encoding model In our daily lives, we perceive a variety of things in different states and environment. For example, when one sees food, one's own state and the state of one's environment vary, such as whether one is hungry or whether there are people around one. Previous studies in cognitive neuroscience, which have explored brain activity under naturalistic conditions, have clarified how various objects and words are expressed in the brain when they are perceived. Research has also been conducted on how one's own state is represented in the brain. However, these previous studies have only defined a few of our own states, and have not clarified how the brain expresses our perceptions of various one’s own state and our surroundings. In this study, we collected blood-oxygen-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) responses from three human subjects while they watched several hours of recordings of a video game. We used a first-person video game as stimuli that can define one’s own state and one's surroundings, and construct a whole-brain voxel-wise encoding model to clarify the representation of information in the brain of various one’s own state and one's surroundings. The prediction accuracy of the model was calculated to verify how well the model captured the brain activity. We also performed a principal component analysis on the model's weight matrix to examine how each state is distributed in cognitive space. Finally, we represented in each subject's brain cortex in which regions of the brain the various states were perceived. When we examined how the various states are encoded in the subjects’ brain, we found that similar states in the video game were perceived as close in the brain's cognitive space. We also found that the perception of one's own state is represented in the superior frontal gyrus and the perception of the surrounding state is represented in the frontal eye field and superior parietal lobule, respectively. Previous studies have shown that the brain's information representation of various perceived objects changes depending on a person's attention and state. Future studies that clarify how the brain's information representation of various objects changes under the different states could improve our understanding of brain activity under naturalistic conditions.		2022年6月30日　13:00～14:00　沖縄コンベンションセンター展示棟　ポスター会場1 1LBA-096 光遺伝学を用いてドーパミン神経を活性化させた時のオレキシン神経の長時間in vivoカルシウムイメージング Long-term in vivo calcium imaging in orexin neurons with optogenetic activation of dopamine neurons 飯嶋大右(1,2,3)、向井康敬(1,2,3)、山中章弘(1,2,3) 1. 名古屋大学、2. 環境医学研究所、3. 神経系分野Ⅱ Daisuke Iijima(1,2,3), Yasutaka Mukai(1,2,3), Akihiro Yamanaka(1,2,3) 1. Nagoya University, 2. Research Institute of Environmental Medicine, 3. Department of Neuroscience 2 Keyword: Orexin, Fiber photometry, Dopamine, Optogenetics Many physiological states, such as sleep-wakefulness, last for a few seconds to several hours. Orexin neurons in the hypothalamus play an important role in the regulation of sleep-wakefulness. These neurons are thought to be active during wakefulness and relatively less active during sleep. Their activities have been reported to be regulated by various neurons. However, most of these studies have been based on in vitro experiments monitoring for just a few minutes. Therefore, it is still unclear what kind of neuronal inputs in vivo can account for the regulation of neuronal activity over a period of seconds to hours, which is the actual duration of sleep-wakefulness state change. In addition, the regulation of orexin neuronal activity over seconds to hours in vivo has not been well observed, and, in particular, the effect of dopamine on orexin neurons has not been examined so far. We previously screened for bioactive substances which regulate activity of orexin neurons using acute brain slices. We found that application of 100 µM dopamine for 2 min increased calcium concentration in orexin neurons for more than one hour. However, the phenomenon was still not examined in vivo. To confirm this in vivo, we established a system in which optogenetics and fiber photometry are performed simultaneously in an identical mouse. We crossed a dopamine transporter (DAT)-Cre recombinase (Cre) mouse line with an orexin-tetracycline transactivator (tTA) mouse line to create mice (DAT-Cre; orexin-tTA) in which two different transgenes can be expressed in dopaminergic (DA) neurons and orexin neurons. By injecting the adeno-associated virus vector (AAV) containing CAG-FLEX-ChrimsonR into these mice, we expressed ChrimsonR, a type of channelrhodopsin, in DA neurons in the ventral tegmendal area. In addition, by injecting AAV-TetO-GCaMP6s, GCaMP6s, a calcium indicator, was expressed exclusively in orexin neurons. Then, calcium imaging of orexin neurons was performed by fiber photometry in combination with 30 seconds of light stimulation of DA neurons. As a result, we observed a short-term decrease in calcium concentration in orexin neurons due to dopamine, which had been reported in vitro. The average of the signal 10~30 seconds after stimulation was significantly decreased compared to the average of the signal before light stimulation. However, a long-term increase in calcium concentration could not be observed. We are now approaching the conditions under which dopamine induces a long-term increase in calcium concentration in orexin neurons in vivo, and are trying to clarify the physiological importance.