Analysis of infromation processing underlining synaptic plasticityof cerebellar Purkinje cells

小脑浦肯野细胞突触可塑性信息处理分析

• 批准号: 12680751
• 负责人: TAKECHI Hajime
• 金额: $ 2.37万
• 依托单位: KYOTO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12680751/
• 关键词: synapse; plasticity; calcium; metabotropic glutamate receptor; IP3 receptor; patch clamp; シナプス可塑性; 小脳; プルキンエ細胞; IP3

Synaptic plasticity is thought to be the underlying process of the learning and memory. To understand the biological background of the memory function, it is important to investigate the process and molecular basis of the synaptic plasticity. Among several chemical mediators, the calcium is the most important messenger to mediate the process of the synaptic plasticity. To learn further about information processing and integration in neuron, the understanding of the function of the metabotropic type neurotransmitter receptor is one of the important issue. I have already reported the involvement of metabotropic glutamate receptor in synaptic plasticity of cerebellar Purkinje cells and the mechanism through the receptor to calcium release from the intracellular calcium store. In this research period, I have studied the interaction of signaling process down stream of metabotropic receptor and intracellular calcium concentration. To see the effect of the intracellular calcium concentration, I used the physiologically important function ; excitability of the membrane which can be assessed by the frequency of the action potential during the current injection. Major results which I obtained during this research period is BK calcium dependent potasium channel as an effector of calcium concentration released via IP3 receptor channel.By the bath application of muscarinic acethylcholine receptor agonist carbacol, the frequency of action potentials elicited by current injection increase when baseline frequency of action potential is low, and decrease when they are high. Decrement of action potentials can be explained by the high intracellular calcium concentration resulting from the high frequency firing. This decrement of firing was blocked by the bath application of BK channel blocker.The delineation of the relationship between metabotrpic type receptor and excitability of membrane will be an important step toward understanding of the synaptic plasticity.

突触可塑性被认为是学习和记忆的基础过程。研究突触可塑性的过程和分子基础对于理解记忆功能的生物学背景具有重要意义。在众多的化学介质中，钙离子是介导突触可塑性过程的最重要的信使。为了进一步了解神经元的信息加工和整合过程，了解代谢型神经递质受体的功能是一个重要的问题。我已经报道了代谢型谷氨酸受体参与小脑浦肯野细胞的突触可塑性，以及通过受体从细胞内钙库释放钙的机制。在本研究期间，我研究了代谢型受体下游信号传导过程与细胞内钙离子浓度的相互作用。为了观察细胞内钙浓度的影响，我使用了生理学上重要的功能;膜的兴奋性，其可以通过电流注射期间动作电位的频率来评估。本研究主要结果是BK钙依赖性钾通道是通过IP 3受体通道释放钙浓度的效应器，通过应用毒蕈碱乙酰胆碱受体激动剂卡巴可，电流注射诱发的动作电位频率在动作电位基线频率较低时增加，在动作电位基线频率较高时减少。动作电位的降低可以通过由高频放电引起的高细胞内钙浓度来解释。这种放电的减少被BK通道阻滞剂所阻断。阐明代谢型受体与膜兴奋性的关系将是理解突触可塑性的重要一步。

项目成果

Hashimoto K, Ichikawa R, Takechi H, et al.: "Roles of glutamate receptor delta 2 subunit (GluRdelta 2) and metabotropic glutamate receptor subtype 1 (mGluR1) in climbing fiber synapse elimination during postnatal cerebellar development"J. Neuroscience. Vo

Hashimoto K、Ichikawa R、Takechi H 等人：“谷氨酸受体 delta 2 亚基 (GluRdelta 2) 和代谢型谷氨酸受体亚型 1 (mGluR1) 在出生后小脑发育过程中攀爬纤维突触消除中的作用”J.

Hashimoto K, Ichikawa R, Takech H, Inoue Y, Aiba A, Sakimura K, Mishina M, Hashikawa T, Konnerth A, Watanabe M, Kano M.: "Roles of glutamate receptor delta 2 subunit (GluRdelta 2) and metabotropic glutamate receptor subtype 1 (mGluR1) in climbing fiber sy

Hashimoto K、Ichikawa R、Takech H、Inoue Y、Aiba A、Sakimura K、Mishina M、Hashikawa T、Konnerth A、Watanabe M、Kano M.：“谷氨酸受体 delta 2 亚基 (GluRdelta 2) 和代谢型谷氨酸受体的作用