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Developmental Switch of Inhibitory Neurotransmitter from GABA to Glycine

抑制性神经递质从 GABA 到甘氨酸的发育转换

基本信息

批准号：
15390065
负责人：
NABEKURA Junichi
金额：
$ 7.1万
依托单位：
National Institute for Physiological Sciences (2004)Okazaki National Research Institutes (2003)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15390065/
关键词：
GABA Development Glycine Transmitter Switch Auditory System スイッチングシナプス

项目摘要

In the late stage of development, a wide spread of synapses re-arrangement take place on the central nervous system. Regarding to these synapse re-arrangements, a wide spread of loss of synapse connection, so-call synapse elimination and a remodeling of synaptic function have been intensely studied. As for developmental change of synaptic function, a large amount of evidences have been reported in the post-synaptic receptors, e.g. subunits changes, and insertion and internalization of receptors. Here, we first reports a new from of remodeling in the developing synapses that a transmitter itself could be switched in the developing auditory system.The lateral superior olive (LSO), an auditory relay center in the brain stem and involved in the orientation of direction of sound coming, receives glycinergic afferents from medial nucleus of trapezoid body (NMTB), in mature rats. However, in immature rats, before onset of hearing, the afferents from NMTB-LSO are largely GABAergic. In developm … More ent, NMTB-LSO synapse changes from GABAergic to glycinergic. Miniature synaptic current analyses revealed that co-release of GABA and glycine from NMTB synapses are well characterized at the transient period of developments. In addition, electron microscopic examination and immunohistochemical study showed that the the transmitter in the terminal gradually changed from GABA to glycine in the first two weeks in development. Thus, these results raise the possibility that the transmitter itself could be change within a single synaptic terminal.For revealing the possible mechanism for this transmitter switch from GABA to glycine, we focused on the developmental change in GABA-B receptors. In immature LSO neurons, there is a dense expression of GABA-B receptor. In development, GABA-B receptor expression disappeared in the LSO neurons. In addition, GABA-B mediated K+ currents and long term depression of GABA/glyicine synapses gradually disappeared in the LSO. Thus, the developmental switch from GABA to glycine release might lead to gradual loss of synapse modulation, and acquirement of solid and fast synaptic transmission by using glycinergic transmission. Less

在发育的后期，中枢神经系统发生了广泛的突触重排。关于这些突触重排，人们对突触连接的广泛丧失、所谓的突触消除和突触功能的重塑进行了深入的研究。关于突触功能的发育变化，已有大量突触后受体的研究报道，如亚单位的变化、受体的插入和内化等。在这里，我们首次报道了发育中的突触重塑的一种新形式，即在发育中的听觉系统中，递质本身可以被切换。在成年大鼠，外侧上橄榄(LSO)是脑干中的一个听觉中继中心，参与声音传入方向的定向，接受来自斜方体内侧核(NMTB)的甘氨酸能传入。然而，在未成熟大鼠中，在听力开始之前，NMTB-LSO的传入大部分是GABA能的。正在开发…此外，NMTB-LSO突触由GABA能变为甘氨酸能。微型突触电流分析表明，在发育的短暂时期，NMTB突触的GABA和甘氨酸的共同释放是很好的特征。此外，电子显微镜检查和免疫组织化学研究表明，在发育的头两周，末端的递质逐渐从GABA转变为甘氨酸。因此，这些结果提出了递质本身可能在单个突触终末内发生变化的可能性。为了揭示这种递质从GABA转换为甘氨酸的可能机制，我们重点研究了GABA-B受体的发育变化。在未成熟的LSO神经元中，GABA-B受体有密集表达。在发育过程中，LSO神经元中GABA-B受体的表达消失。此外，GABA-B介导的钾电流和GABA/甘氨酸突触的长时程抑制在LSO中逐渐消失。因此，从GABA到甘氨酸释放的发育转换可能导致突触调节的逐渐丧失，并通过甘氨酸能传递获得可靠而快速的突触传递。较少

项目成果

期刊论文数量（44）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Mizoguchi Y, Kanematsu T, Hirata M, Nabekura J: "A rapid increase in the total number of cell surface functional GABA_A receptors induced by brain-derived neurotrophic factor in rat visual cortex"Journal Biological Chemistry. 278. 44097-44102 (2003)

Mizoguchi Y、Kanematsu T、Hirata M、Nabekura J：“大鼠视觉皮层脑源性神经营养因子诱导的细胞表面功能性 GABA_A 受体总数快速增加”《生物化学》杂志。

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Mizoguchi Y, Nabekura J: "Sustained intracellular Ca^<2+> elevation induced by a brief BDNF application in rat visual cortex neurons receptors induced by brain-derived neurotrophic factor in rat"Neuroreport. 14. 1484-1483 (2003)

Mizoguchi Y，Nabekura J：“在大鼠脑源性神经营养因子诱导的大鼠视觉皮层神经元受体中，短暂应用BDNF诱导细胞内Ca 2+ 持续升高”Neuroreport。

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0
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Potentiation of NMDA receptor-mediated synaptic responses by microglia.

小胶质细胞增强 NMDA 受体介导的突触反应。

DOI：
发表时间：
2003
期刊：
Brain Res Mol Brain Res. 119
影响因子：
0
作者：
Moriguchi S;Mizoguchi Y;Tomimatsu Y;Hayashi Y;Kadowaki T;Kagamiishi Y;Katsube N;Yamamoto K;Inoue K;Watanabe S;Nabekura J;Nakanishi H.
通讯作者：
Nakanishi H.

The action of BDNF on GABAA currents changes from potentiating to suppressing during maturation of rat hippocampal CA1 pyramidal neurons