GABAergic inhibition regulates developmental synapse elimination in the cerebellum

GABA 能抑制调节小脑发育突触消除

• 批准号: 21700346
• 负责人: NAKAYAMA Hisako
• 金额: $ 2.83万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21700346/
• 关键词: シナプス; 神経回路; 発達; 小脳; プルキンエ細胞; 登上線維; シナプス刈り込み; GABA; パッチクランプ; 神経科学

Functional neural circuit formation during development involves massive elimination of redundant synapses. In the cerebellum, one-to-one connection from excitatory climbing fiber (CF) to Purkinje cell (PC) is established by elimination of early-formed surplus CFs. This process depends on glutamatergic excitatory inputs, but contribution of GABAergic transmission remains unclear. Here we demonstrate impaired CF synapse elimination in mouse models with diminished GABAergic transmission by mutation of a single allele for the GABA synthesizing enzyme GAD67, conditional deletion of GAD67 from PCs and GABAergic interneurons or pharmacological inhibition of cerebellar GAD activity. The impaired CF synapse elimination was rescued by enhancing GABAA receptor sensitivity in the cerebellum by locally applied diazepam. Our electrophysiological and Ca^<2+> imaging data suggest that GABAA receptor-mediated inhibition onto the PC soma from molecular layer interneurons influences CF-induced Ca^<2+> transients in the soma and regulates CF synapse elimination from postnatal day 10 (P10) to around P16.

发育过程中功能性神经回路的形成涉及大量消除冗余突触。在小脑，从兴奋性攀爬纤维（CF）到浦肯野细胞（PC）的一对一连接是通过消除早期形成的多余CF建立的。这一过程依赖于多巴胺能兴奋性输入，但GABA能传递的贡献尚不清楚。在这里，我们证明了受损的CF突触消除在小鼠模型中减少GABA能传递的突变的一个单一的等位基因的GABA合成酶GAD 67，条件删除GAD 67从PC和GABA能中间神经元或药理学抑制小脑GAD活性。通过局部应用地西泮增强小脑中GABAA受体的敏感性来挽救受损的CF突触消除。我们的电生理学和Ca^<2+>成像数据表明，GABAA受体介导的对PC索马胞体的抑制作用影响CF诱导的索马胞体中的Ca^<2+>瞬变，并调节出生后第10天（P10）至P16左右CF突触的消除。

项目成果

Analysis of climbing fiber inputs to Purkinje cells in the developing rat cerebellum in vivo.

分析体内发育中的大鼠小脑中浦肯野细胞的攀爬纤维输入。

• 发表时间: 2009
• 作者: K.Yamamoto;J.Ando;Kawamura Y
• 通讯作者: Kawamura Y

GABAwegic inhibition onto Purkinje cell soma is crucial for climbing fiber synapse elimination in developing cerebellum

对浦肯野细胞体的 GABAwegic 抑制对于小脑发育过程中攀爬纤维突触的消除至关重要

• 发表时间: 2009
• 作者: 中山寿子;宮崎太輔;橋本浩一;柳川右千夫;小幡邦彦;渡辺雅彦;狩野方伸
• 通讯作者: 狩野方伸

GABAergic inhibition onto Purkinje cell soma is crucial for climbing fiber synapse elimination in developing cerebellum

对浦肯野细胞体的 GABA 能抑制对于小脑发育过程中攀爬纤维突触的消除至关重要

• 发表时间: 2009
• 作者: 中山寿子;宮崎太輔;橋本浩一;柳川右千夫;小幡邦彦;渡辺雅彦;狩野方伸;中山寿子
• 通讯作者: 中山寿子