Synaptic receptors and plasticity

突触受体和可塑性

• 批准号: 07278102
• 负责人: MISHINA Masayoshi
• 金额: $ 179.46万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research on Priority Areas
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-07278102/
• 关键词: 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

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.

我们通过培养谷氨酸受体（GluRs）缺失突变小鼠，研究突触可塑性与神经发育、学习和记忆的关系。GluRε1亚基突变小鼠在Morris水迷宫中表现出海马LTP下降和空间学习障碍。GluRε2亚基突变阻碍了脑干三叉核中与须相关的神经元桶状结构的形成和海马突触的可塑性。GluRδ2亚基选择性定位于小脑浦肯野细胞，对小脑发育、运动协调、运动学习、平行纤维-浦肯野细胞突触的稳定性和多攀爬纤维（CF）的消除至关重要。代谢性GluR1突变小鼠在小脑LTD、联合眨眼条件反射和CF消除方面存在缺陷。在多发CFs的PKCγ突变小鼠中，眨眼调节是正常的。这些结果表明，突触可塑性是某种形式的学习和记忆的细胞基础。他们还认为，在大脑发育和大脑高级功能过程中，GluRs在神经网络形成中起着重要作用，这意味着这些过程具有共同的分子机制。

项目成果

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Tempia, F.：“通过具有‘低’钙渗透性的神经元 AMPA 受体通道的钙电流分数。”J.Neurosci.15 (1996)。

Ito,I.: "Age-dependent reductuion of hippocampal LTP in mice lacking NMDA receptor ε1 subuint." Neurosci.Lett.203. 69-71 (1996)

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杉山博之: "メタボトロピック・グルタミン酸受容体の特性と海馬シナプスにおける役割" 日本生理学雑誌(J. Physiol. Soc. Jpn.). 57. 253-260 (1995)

Hiroyuki Sugiyama：“代谢型谷氨酸受体的特征及其在海马突触中的作用”J. Physiol. Jpn. 57. 253-260 (1995)

Yamakura, T.: "Effects of propofol on various AMPA-, kainate- and NMDA-selective glutamate receptor channels expressed in Xenopus oocytes"Neuroscience Letters. 188. 187-190 (1995)

Yamakura, T.：“异丙酚对非洲爪蟾卵母细胞中表达的各种 AMPA、红藻氨酸和 NMDA 选择性谷氨酸受体通道的影响”神经科学快报。