| Project/Area Number |
07278102
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| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
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| Allocation Type | Single-year Grants |
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| Research Institution | The University of Tokyo |
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Principal Investigator |
MISHINA Masayoshi University of Tokyo, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (80144351)
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| Co-Investigator(Kenkyū-buntansha) |
WATANABE Masahiko Hokkaido University Graduate School of Medicine, Professor, 大学院・医学研究科, 教授 (70210945)
UMEMORI Hisashi University of Tokyo, Institute of Medical Science, Assistant Professor, 医科学研究所, 助手 (20242117)
YAGI Takeshi Okazaki, National Institute for Physiological Science, Associate Professor, 生理学研究所, 助教授 (10241241)
KANO Masanobu Kanazawa University, School of Medicine, Professor, 医学部, 教授 (40185963)
MANABE Toshiya University of Tokyo, Graduate School of Medicine, Lecturer, 大学院・医学系研究科, 講師 (70251212)
崎村 建司 新潟大学, 脳研究所, 教授 (40162325)
杉山 博之 九州大学, 理学部, 教授 (20124224)
高橋 智幸 東京大学, 医学部, 教授 (40092415)
二木 宏明 東京大学, 大学院・人文,社会系研究科, 教授 (10073074)
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| Project Period (FY) |
1995 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥280,400,000 (Direct Cost: ¥280,400,000)
Fiscal Year 1998: ¥60,500,000 (Direct Cost: ¥60,500,000)
Fiscal Year 1997: ¥61,200,000 (Direct Cost: ¥61,200,000)
Fiscal Year 1996: ¥74,100,000 (Direct Cost: ¥74,100,000)
Fiscal Year 1995: ¥84,600,000 (Direct Cost: ¥84,600,000)
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| Keywords | NMDA receptor / glutamate receptor / synaptic plasticity / memory / learning / hippocampus / cerebellum / synapse formation / LTP / NMDA受容体チャネル / リン酸化 / 小脳プルキンエ細胞 / 神経回路網 / G蛋白質 / ノックアウトマウス / 運動失調 |
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| Research Abstract |
We investigated the relationship of synaptic plasticity to neural development, learning and memory by generating mutant mice lacking glutamate receptors (GluRs). The GluRε1 subunit mutant mice showed the decreased hippocampal LTP and impaired spatial learning in the Morris water maze. The GluRε2 subunit mutation hindered the formation of the whisker-related neuronal barrelette structure in the brainstem trigeminal nucleus and synaptic plasticity in the hippocampus. The GluRδ2 subunit selectively localized in cerebellar Purkinje cells was essential for cerebellarLTD, motor coordination, motor learning, stability of parallel fiber-Purkinje cell synapses and elimination of multiple climbing fibers (CF) during development. Metabotropic GluR1 mutant mice were defective in cerebellar LTD, associative eyeblink conditioning and CF elimination. Eyeblink conditioning was normal in PKCγ mutant mice with multiple CFs. These results suggest that synaptic plasticity is the cellular basis of a certain form of learning and memory. They also suggest that GluRs play important roles in neural network formation during brain development and in higher brain function, implying that these processes share common molecular mechanisms.
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