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Molecular and cellular basis of synaptic function

突触功能的分子和细胞基础

基本信息

批准号：
03304026
负责人：
OZAWA Seiji
金额：
$ 7.1万
依托单位：
Gunma University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Co-operative Research (A)
财政年份：
1991
资助国家：
日本
起止时间：
1991 至 1993
项目状态：
已结题

项目摘要

In this study, we investigated molecular and cellular basis of synaptic transmission in the three aspects, namely 1)molecular structure and electrophysiological properties of receptor channels, 2)regulation of calcium metabolism and its relation to transmitter release, and 3)mechanism of synaptic plasticity. The main results are as follows.1.Molecular structure and functional properties of receptor channelsMishina has identified four modulatory subunits (epsilon1-epsilon4)of the mouse NMDA receptor by cloning and expression of cDNAs. This molecular diversity of the epsilon subunits underlies the functional heterogeneityb of the NMDA receptor. Ozawa has coupled patch-clamp recordings and reverse transcription followed by PCR amplification, and identified the subunit composition of the Ca^<2+>-permeable AMPA receptor at the single cell level. Takahashi has expressed fetal- and adult-type glycine receptor cDNAs, and shown that the mean open time of the adult-type receptor has a shorter op … More en time. This result is consistent with that the decay time of glycinergic IPSCs becomes shorter during postnatal development.2.Calcium metabolism and transmitter releaseKuba has measured intracellular Ca^<2+> concentration in sympathetic neurons and presented the evidence that the activation of calcium-induced calcium release occurs as a result of Ca^<2+>-influx through voltage-dependent Ca^<2+> channels. Yawo has shown that Ca^<2+>-influx through the N-type Ca^<2+> channel mediates transmitter release from the chick ciliary presynaptic terminal. Tachibana has demontrated that the transmitter of the ganglion cell of the goldfish retina is L-gluatamate, and that this transmitter release is mediated by the activation of L-type Ca^<2+> channels.3.Mechanism of synaptic plasticityHirano has investigated the mechanism of long-term depression (LTD) of the synaptic transmission between cerebellar granule and Purkinje cells, presenting the evidence that the adtivation of metabotropic glutamate receptor (mGluR1) is involved in the induction of LTD. Less

本研究从受体通道的分子结构和电生理特性、钙代谢的调节及其与递质释放的关系、突触可塑性机制三个方面探讨了突触传递的分子和细胞基础。主要研究结果如下：1.受体通道的分子结构和功能特性Mishina等人通过克隆和表达小鼠NMDA受体的cDNA，鉴定出四个调节亚基（ε 1-ε 4）。NMDA亚基的这种分子多样性是NMDA受体功能异质性的基础。Ozawa将膜片钳记录和逆转录结合起来，随后进行PCR扩增，并在单细胞水平上鉴定了Ca^2+可渗透AMPA受体的亚基组成。Takahashi已经表达了胎儿型和成人型甘氨酸受体cDNA，并表明成人型受体的平均开放时间比胎儿型受体短。 ...更多信息准时。这一结果与甘氨酸能IPSCs在出生后发育过程中衰减时间变短的结论相一致。2.钙代谢和递质释放Kuba测量了交感神经元细胞内Ca^<2+>浓度，并提出证据表明，钙诱导的钙释放的激活是通过电压依赖性Ca^<2 +>通道的Ca^<2 +>内流的结果。Yawo已经证明，通过N型Ca^<2 +>通道的Ca ^<2 +>内流介导了鸡纤毛突触前末梢的递质释放。Tachibana等人证明了金鱼视网膜神经节细胞的递质是L-谷氨酸，这种递质的释放是通过L型Ca^2+通道的激活来介导的。3.突触可塑性的机制Hirano等人研究了小脑颗粒和浦肯野细胞之间突触传递的长期抑制（LTD）机制，提出了代谢型谷氨酸受体（mGluR 1）的活化参与LTD诱导的证据。