学習・長期記憶2 Learning and Long-term Memory 2
O2-8-5-1 脳の可塑性と摂食の機能連関 Functional relationship between food intake and brain plasticity ○粟生修司2, 大村裕1, 森口茂樹3, 福永浩司3 ○Yutaka Oomura1, Shuji Aou2, Shigeki Moriguchi3, Koji Fukunaga3 九州大院・医・統合生理1, 九工大院・生命体・脳情報2, 東北大院・薬・薬理3 Dept Integr Phusiol, Kyushu Univ, Fukuoka1, Dept Brain Sci & Technol, Kyushu Inst Technol, Kitakyushu2, Dept Pharmacol, Sch Farmacy, Tohoku Univ, Sendai3 Acidic fibroblast growth factor (aFGF) and leptin are released from the ependymal cells in the third cerebral ventricle and adipose tissue respectively and enter into the hypothalamus and hippocampus during food intake. Both of them suppress food intake and facilitate the hippocampal long term potentiation and releavant spatial memory. In the present study, we demonstrate the glucose increased in the brain during FI also facilitates these memory and learning processes. During food intake 3 mM G concentration in CSF becomes twice. When 6 mM glucose injected into the rat hippocampal CA1 region behavioral learning and memory are facilitated. In CA1 slice with 3 mM glucose in Ringer solution EPSPs amplitudes generated by the Schaffer collateral/commissural stimulation markedly increased in 6 mM glucose. The paired-pulse facilitation experiments indicated augmentation of transmitter release by 6 mM glucose. The postsynaptic EPSPs amplitudes were significantly increased in 6 mM glucose associated with the augementations of the phosphorylations of CAMKII and PKC. The increased EPSPs amplitudes were also due to the increase of the presynaptic synapsin phosphorelation. Transmitter evoked postsynaptic currents were measured in CA1 neurons by electrophoretic applications of NMDA and AMPA to the apical dendrites of the pyramidal neurons. NMDA and AMPA evoked currents were significantly augmented by elevation to 6 mM glucose. Notably high frecuency stimulation of the Schaffer pathway failed to induce LTP in the CA1 region in 3 mM glucose but facilitated LTP in 6 mM G. The LTP induction in the 6 mM glucose was associated with further increase in CAMKII and PKC autophosphorylations. Taken together food intake is valuable for the brain plasticity.	O2-8-5-2 発達期のRacGAP α2キメリンは、成体における正常な海馬依存的学習を成立させる RacGAP α2-chimaerin functions during development to establish normal hippocampus-dependent learning in adulthood ○岩田亮平1,2, 水野秀信1,2, 岩間瑞穂3, 後藤大道3, 田中三佳3, 糸原重美3, 岩里琢治1,2 ○Ryohei Iwata1,2, Hidenobu Mizuno1,2, Mizuho Iwama3, Hiromichi Goto3, Mika Tanaka3, Shigeyoshi Itohara3, Takuji Iwasato1,2 遺伝研・形質遺伝1, 総研大2, 理研BSI・行動遺伝3 Division of Neurogenetics, National Institute of Genetics (NIG), Shizuoka, Japan1, Department of Genetics, the Graduate University for Advanced Studies (SOKENDAI), Shizuoka, Japan2, Laboratory for Behavioral Genetics, RIKEN Brain Science Institute, Saitama, Japan3 Morphological features of dendritic spines are basis of neural circuit function and animal behavior, and their abnormalities underlie cognitive impairment and neuropsychiatric disorders. The small GTPase Rac plays important roles in morphogenesis of dendritic spines by modulating the organization of the actin cytoskeleton. However, upstream signaling of Rac in spine morphogenesis is poorly understood, especially in vivo. Here we report α2-chimaerin, a Rac GTPase-activating protein (GAP), is a key regulator of spine morphology and function. By generating series of conditional and isoform-specific α-chimaerin knockout mouse lines, we showed that expression of α2-chimaerin in the developing dorsal telencephalon affect on hippocampus-dependent learning in adult mice. Deletion of α2-chimaerin during development leads to increased size and density of spines throughout life, and enhanced synaptic transmission in the adult hippocampus. Moreover, we found that α2-chimaerin mediates ephrinA3/EphA4 forward signaling-dependent spine retraction in slice culture of developing hippocampus. Our findings suggest that α2-chimaerin establish normal cognitive abilities in adulthood by negatively regulating spinogenesis in the developing brain.
O2-8-5-3 放射線照射を受け認知機能が低下したラットでは海馬歯状回の光刺激後に誘導されるCA3領域のBOLD反応が有意に低下していた The decrease in CA3 BOLD response after the optic stimulation of the dentate gyrus in ChR2-expressing rats suffered from the radiation exposure ○阿部欣史1, 関野正樹2, 今岡遼太1, 大崎博之3, 寺園泰4, 尾田正二1, 三谷啓志1, 深澤有吾5, 八尾寛6, 久恒辰博1 ○Yoshifumi Abe1, Masaki Sekino2, Ryota Imaoka1, Hiroyuki Ohsaki3, Yasushi Terazono4, Shoji Oda1, Hiroshi Mitani1, Yugo Fukazawa5, Hiromu Yowo6, Tatsuhiro Hisatsune1 東京大 新領域 先端生命1, 東京大 工学 電子情報2, 東京大 新領域 先端エネルギー3, 東京大 工学 計数工学4, 名古屋大 医 分子細胞5, 東北大 生命 脳機能解析6 Dept of Integrated Biosci, Grad Sch of Frontier Sci, Univ of Tokyo, Chiba, Japan1, Dept of Elect Eng and Info Systems, Grad Sch of Eng, Univ of Tokyo, Tokyo, Japan2, Dept of Advanced Energy, Grad Sch of Frontier Sci, Univ of Tokyo, Chiba, Japan3, Dept of Math Eng and Info, Grad Sch of Eng, Univ of Tokyo, Tokyo, Japan4, Dept Anatomy and Mol Cell Biol, Nagoya Univ Sch Med, Nagoya, Japan5, Dept of Dev and Neurosci, Grad Sch of Life Sci, Tohoku Univ, Sendai, Japan6 Hippocampal-dependent cognitive function, especially spatial memory, is impaired by the radiation exposure due to the reduction of hippocampal neurogenesis. It has been demonstrated that the cognitive function transiently decreased after the radiation exposure to the brain, which may be related to the transient decline in the degree of adult neurogenesis. Actually, we observed the deficit in spatial memory function just at 6 weeks, but not 1 week or 4 months after the radiation exposure to both rats and mice. To elucidate the alteration of the hippocampal activity in rodents with the cognitive impairment, in this study, Channelrhodopsin-2 expressing transgenic rats were exposed with a single dose of 10 Gy gamma-ray radiation to the brain and we conducted optogenetical fMRI analysis 6 weeks after the radiation. Alpha-chloralose-anesthetized rats which had been attached with optic fiber for the dentate gyrus (DG) stimulation were placed in 4.7T animal MRI scanner (Varian). BOLD fMRI data was collected during the optical stimulation delivered by 473 nm laser. In control non-irradiated rats (n=6), the optical stimulation at the DG evoked 2.07±0.14 % BOLD activation in the CA3 area. However, in rats exposed with the radiation exposure, the degree of BOLD response in the CA3 area was significantly weaker to 0.51±0.13 % (n=6; P<0.001) than that in control rats while the degree of BOLD response in the DG was equivalent. These results suggest that the CA3 response evoked by optical stimulation at the DG was impaired by the radiation exposure, probably due to the inhibition of the synaptic transmission from the DG to the CA3 by the decrease in the newborn neurons, which would affect hippocampal-dependent cognitive function.	O2-8-5-4 SCOPが関与する物体認識記憶のサーカディアン制御機構 Molecular mechanism of SCOP-related circadian memory formation for novel objects ○清水貴美子1, 小林洋大1, 中辻英里香1, 深田吉孝1 ○Kimiko Shimizu1, Yodai Kobayashi1, Erika Nakatsuji1, Yoshitaka Fukada1 東京大学大学院理学系研究科生物化学専攻1 Dept Biophys and Biochem, Grad School of Science, Univ of Tokyo, Tokyo1 Evidence from previous studies demonstrates that circadian rhythms affect memory formation. However it is not yet clear if the internal clock regulates the efficiency of the memory formation, and there is no molecular-based evidence that connects the memory formation and circadian rhythms. We performed novel object recognition tests on mice over the circadian time. Long-term memory varied in a circadian manner and hence it seems to be controlled by the endogenous circadian clock. In fact, electrolytic lesion of the suprachiasmatic nucleus (SCN), which has been established as the master circadian clock, effectively disrupted the circadian rhythm of long-term memory formation. We are focusing on SCOP and related molecules to find a molecular process that connects the circadian clock with the memory formation. SCOP is expressed in a circadian manner in the mouse SCN, and SCOP negatively regulates K-Ras function and its downstream ERK/MAPK pathway. In the hippocampus, SCOP is critical for long-term memory formation for novel objects. These data together suggest that SCOP-ERK pathway could be a key for circadian control for the long-term memory formation in the hippocampus. We found that SCOP protein levels in the raft fraction in the hippocampus oscillate in a circadian manner. SCOP knockdown in the hippocampus by shRNA expression lentivirus attenuated circadian oscillation of the long-term memory for novel objects. SCOP knockout mice did not show circadian oscillation of the long-term memory for novel objects. These data suggest that circadian regulated long-term memory formation for novel objects is dependent on SCOP protein levels in the rafts of the hippocampus.

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