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.

我们通过生成缺乏谷氨酸受体（GluRs）的突变小鼠来研究突触可塑性与神经发育、学习和记忆的关系。GluRε1亚基突变小鼠的海马LTP减少，并且GluRε2亚基突变阻碍了莫里斯的空间学习。脑干三叉神经核中与晶须相关的神经元桶状结构的形成和海马中的突触可塑性。选择性定位于小脑浦肯野细胞中的 GluRδ2 亚基对于小脑LTD、运动协调、运动学习、平行纤维浦肯野细胞突触的稳定性以及发育过程中多个攀爬纤维（CF）的消除至关重要。在具有多个 CF 的 PKCγ 突变小鼠中，眨眼调节和 CF 消除是正常的。他们还表明，突触可塑性是某种形式的学习和记忆的细胞基础，GluR 在大脑发育过程中的神经网络形成和高级大脑功能中发挥着重要作用，这意味着这些过程具有共同的分子机制。

项目成果

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)

Hori,Y.: "Long-lasting facilitation induced by serotonin in superficial dorsal horn neurones of rat spinal cord." J.Physiol.492. 867-876 (1996)

Hori,Y.：“血清素对大鼠脊髓浅表背角神经元产生持久的促进作用。”

Minami,T.: "Absence of prostglandin E_2-induced hyperalgesia in NMDA receptor ε subunit knockout mice." Br.J.Pharmacol.120. 1522-1526 (1997)

Minami, T.：“NMDA 受体 ε 亚基敲除小鼠中不存在前列腺素 E_2 诱导的痛觉过敏。Br.J.Pharmacol.120 (1997)。

Ito, I.: "Synapse-selective impairment of NMDA receptor functions in mice lacking NMDA receptor ε1 or ε2 subunit"Neurosci. Lett.. 203. 69-71 (1996)

Ito, I.：“缺乏 NMDA 受体 ε1 或 ε2 亚基的小鼠中 NMDA 受体功能的突触选择性损伤”Neurosci. Lett.. 203. 69-71 (1996)

Chen, C.: "Impaired motor coordination correlates with persistent multiple climbing fiber innervation in PKC_γ mutant mice"Cell. 83. 1233-1242 (1995)

Chen, C.：“运动协调受损与 PKC_γ 突变小鼠的持续多攀爬纤维神经支配相关”Cell。 83. 1233-1242 (1995)