神経化学

神経化学優秀賞受賞者企画シンポジウム分子・細胞種・神経回路に基づく記憶学習メカニズムの包括的な理解

7月6日（木）　14:20-16:20　Room F 1SY⑦-1 記憶固定に関わるアストロサイトの全脳解析 Brain-wide astrocyte ensembles for memory consolidation 長井　淳理化学研究所　脳神経科学研究センター Jun Nagai RIKEN Center for Brain Science Neural circuits are composed of a variety of cellular activities that are distributed throughout the brain, spinal cord, and peripheral regions, dynamically regulating the entire body system via sub- and supra-second signals. This complexity is due in part to the coexistence of multiple cell types within circuits. Astrocytes, which tile the entire central nervous system, play crucial roles in maintaining brain homeostasis. Recent studies using single-cell RNA sequencing have identified molecular diversity among astrocytes. However, it remains unclear whether functionally distinct astrocyte ensembles regulate specific behaviors. In this study, we aim to address this question using advantageous tools to quantify astrocyte anatomy, molecular properties, and causal impact in response to distinct valence-experiences. Our findings demonstrate that anatomically distinct astrocyte ensembles respond to different valence-stimuli and have unique molecular phenotypes. Whole brain mapping revealed distinct distributions of activated astrocytes in response to appetitive or aversive experience. Our data suggest that astrocytes responding to reward and aversion may be anatomically and molecularly distinct ensembles. We will also report our pilot experiments to elucidate the circuits and behavioral functions of these astrocytes.		7月6日（木）　14:20-16:20　Room F 1SY⑦-2 ドコサヘキサエン酸による記憶学習能力向上の分子メカニズム Molecular mechanism of improving memory and learning ability by docosahexaenoic acid 矢尾　育子, 鳥山　道則関西学院大学 Ikuko Yao, Michinori Toriyama Kwansei Gakuin University Docosahexaenoic acid (DHA) is an n-3 essential unsaturated fatty acid that is a component of neuronal membrane phospholipids, and extremely important for normal brain development. Conversely, DHA deficiency induces age-related brain function abnormalities, Alzheimer's disease, and peroxisomal disease. Recently, it has been reported that unsaturated fatty acids such as DHA improve memory/learning ability and the pathophysiology of Alzheimer's disease. However, the detailed molecular mechanism is still unknown. In this study, we analyzed the effect of DHA on the improvement of brain function, focusing on the activation of GPR40, one of the DHA receptors, using mice: DHA administration significantly increased dendritic spine density. Subsequently, short-term memory was evaluated by a behavioral test using a Y-maze, and the alternation behavior rate was significantly increased with the administration of DHA. Those effects were avoided by the GPR40 inhibitor. Our results suggest that DHA increased spine density and enhanced learning, and DHA promoted dendrite spine formation. DHA could contribute to the improvement of short-term memory by promoting the formation of dendritic spines through the activation of GPR40.

7月6日（木）　14:20-16:20　Room F 1SY⑦-3 後頭頂葉による経験依存的な記憶更新制御 A cortical cell ensemble in the posterior parietal cortex controls experience-dependent memory updating 鈴木　章円^1,2, 小杉　桜子¹, 村山　絵美^1,2, 大川　宜昭³, 今野　歩⁴, 平井　宏和⁴, 井ノ口　馨^1,2 1. 富山大学　学術研究部医学系, 2. 富山大学　アイドリング脳科学研究センター, 3. 獨協医科大学　先端医科学統合研究施設　先端医科学研究センター　認知・記憶研究部門, 4. 群馬大学大学院　医学系研究科　脳神経再生医学分野 Akinobu Suzuki^1,2, Sakurako Kosugi¹, Emi Murayama^1,2, Noriaki Ohkawa³, Ayumu Konno⁴, Hirokazu Hirai⁴, Kaoru Inokuchi^1,2 1. Department of Biochemistry, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan, 2. Research Center for Idling Brain Science, University of Toyama, Toyama, Japan, 3. Division for Memory and Cognitive Function, Research Center for Advanced Medical Science, Comprehensive Research Facilities for Advanced Medical Science, Dokkyo Medical University, Tochigi, Japan, 4. Department of Neurophysiology and Neural Repair, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan When processing current sensory inputs, animals refer to related past experiences. Current information is then incorporated into the related neural network to update previously stored memories. However, the neuronal mechanism underlying the impact of memories of prior experiences on current learning is not well understood. Here, we found that a cellular ensemble in the posterior parietal cortex (PPC) that is activated during past experience mediates an interaction between past and current information to update memory through a PPC-anterior cingulate cortex circuit in mice. Moreover, optogenetic silencing of the PPC ensemble immediately after retrieval dissociated the interaction without affecting individual memories stored in the hippocampus and amygdala. Thus, a specific subpopulation of PPC cells represents past information and instructs downstream brain regions to update previous memories.		7月6日（木）　14:20-16:20　Room F 1SY⑦-4 哺乳類における記憶学習能力の日周リズム Diurnal rhythm of learning and memory in mice and nonhuman primates 清水　貴美子^1,2 1. 東京医科歯科大学　難治疾患研究所, 2. 東京大学　疾患生命工学センター Kimiko Shimizu^1,2 1. Tokyo Medical Dental Univ, Tokyo, Japan, 2. Center for Disease Biol and integrative Medicine, Univ. of Tokyo, Tokyo, Japan Learning and memory depend on the time of day in various organisms. We found that long-term recognition memory is circadian-regulated and blunted by disruption of the hippocampal clock in nocturnal mice. SCOP (PHLPP1β) is a key molecule regulating hippocampus-dependent long-term memory for objects. The amounts of SCOP exhibit robust circadian changes, and SCOP knockdown in the hippocampal CA1 impairs long-term memory at night. We concluded that long-term memory formation in recognition memory is regulated by the circadian clock through SCOP in the hippocampal CA1 in mice. Given that the circadian rhythm is conserved across species with diurnal/nocturnal habits, we used diurnal Japanese macaques to see the time of day affects memory performance. We found the diurnal variation of declarative memory in Japanese macaques. The middle of the daytime is the most effective time for memory performance during the light period. To assess whether SCOP is involved in declarative memory performance, we interfered with SCOP expression by using lentiviral vector. Scop knockdown in the hippocampus abrogated the memory performance in the middle of the daytime. Our results implicate that SCOP in the hippocampus is necessary for the diurnal rhythm of the memory system and that the SCOP-dependent memory regulation system could be conserved in mammals.

7月6日（木）　14:20-16:20　Room F 1SY⑦-5 海馬における日々のエピソード記憶を構成する原理 Principle of organization of daily episodic memories in the hippocampus 大川　宜昭獨協医科大学　先端医科学統合研究施設 Noriaki Ohkawa Comprehensive Research Facilities Adv Med Sci, Dokkyo Med Univ, Tochigi, Japan Memories of novel episodes in daily life are stored through a subset of neurons, termed engram cells. However, how different sets of engram cells are selected for current and next episodes remains unclear. To elucidate organization of engram cells, we established a unique imaging system to identify engram cells and to record the Ca²⁺ events corresponding to the activity of engram cells and non-engram cells during memory processing of a novel episodic event. By this system, we found out that information of one episodic experience is composed of several hippocampal engram sub-ensembles defined by individual synchronous activities, and a portion of the engram sub-ensemble activities survive through from post-experience sleep to retrieval session. On the other hand, several ensemble activities constructed from non-engram cells during post-learning offline periods were sharing features of engram ensembles and behaved to represent next new learning. These results propose that a circulation of appearance of ensemble activities of engram and non-engram cells is principle of organization of daily episodic memories in the hippocampus.		7月6日（木）　14:20-16:20　Room F 1SY⑦-6 Eph-ephrin signal is crucial for cognitive modules in medial entorhinal cortex 北村　貴司テキサス大学サウスウェスタン医学センター Takashi Kitamura University of Texas Southwestern Medical Center Topographic arrangement of neurons is thought to mediate brain function. Hexagonally arranged pyramidal cell clusters and surrounding stellate cells formed evolutionally conserved anatomical modules in layer II of the mammalian medial entorhinal cortex (MECII), called the island-ocean structure. MECII neurons represent an animal’s location through the collective activity of multiple grid cells from distinct grid modules with the discrete value of spatial scale and orientation. Although several studies suggest that the interaction with coordinated distance on the local pre-wired networks underlies the modular grid coding, the contribution of the anatomical module to the modular grid coding is still unclear. Here we identified ephrin-B2 as a key molecule for the island structure as well as grid modules. The island cells cluster was selectively disorganized by the genetic attenuation of ephrin-B2 signaling. Further analysis suggested that ephrin-B2 controls tangential migration and promotes clustered radial migration in the postnatal MEC. Calcium imaging revealed that altered scale relations across grid modules and lack of the modular correlation structure of the MECII network in ephrin-B2-deficient mice. We show the first evidence that the anatomical module provides a geometrical platform for modular spatial information processing in mammalian MEC.