GAD67-mediated GABA Synthesis and Signaling Impinges on Directing Basket Cell Axonal Projections Toward Purkinje Cells in the Cerebellum
GAD67-mediated GABA Synthesis and Signaling Impinges on Directing Basket Cell Axonal Projections Toward Purkinje Cells in the Cerebellum
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GAD67 介导的 GABA 合成和信号传导影响引导篮细胞轴突投射向小脑浦肯野细胞
DOI：
10.1007/s12311-021-01334-8
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Yanagawa Yuchio
中科院分区：
文献类型：
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作者：
Miwa Hideki;Kobayashi Ken;Hirai Shinobu;Yamada Mitsuhiko;Watanabe Masahiko;Okado Haruo;Yanagawa Yuchio
γ-氨基丁酸（GABA）是中枢神经系统中的一种主要抑制性神经递质，由谷氨酸脱羧酶（GAD）的两种亚型GAD 65和GAD 67合成。GABA可能在脑发育过程中作为营养因子，但其对小脑神经回路的发育和成熟的贡献尚不清楚。为了了解GABA在小脑组织中的作用以及在运动协调和平衡中的相关功能，我们检查了GAD 65常规敲除（KO）小鼠和GAD 67在小白蛋白表达神经元中被消除的小鼠（PV-Cre; GAD 67 flox/mouse）。我们发现异常的亚细胞定位的Shaker型K通道Kv1.1在篮子细胞侧支PV-Cre; GAD 67 flox/mouse和异常的预测从篮子细胞浦肯野细胞在两种小鼠品系。我们还发现PV-Cre; GAD 67 flox/p53小鼠中的篮状细胞终末与浦肯野细胞的突触特性发生了改变。此外，PV-Cre; GAD 67 flox/p53小鼠在转棒测试中表现出异常的运动协调。这些结果表明，GABA信号在小脑是至关重要的篮细胞和浦肯野细胞之间建立适当的连接，并与运动协调小鼠。
Gamma-aminobutyric acid (GABA) is a major inhibitory neurotransmitter in the central nervous system, synthesized by two isoforms of glutamate decarboxylase (GAD): GAD65 and GAD67. GABA may act as a trophic factor during brain development, but its contribution to the development and maturation of cerebellar neural circuits is not known. To understand the roles of GABA in cerebellar organization and associated functions in motor coordination and balance, we examined GAD65 conventional knock out (KO) mice and mice in which GAD67 was eliminated in parvalbumin-expressing neurons (PV-Cre;GAD67flox/floxmice). We found aberrant subcellular localization of the Shaker-type K channel Kv1.1 in basket cell collaterals ofPV-Cre;GAD67flox/floxmice and abnormal projections from basket cells to Purkinje cells in both mouse strains. We also found that altered synaptic properties of basket cell terminals to Purkinje cells inPV-Cre;GAD67flox/floxmice. Furthermore,PV-Cre;GAD67flox/floxmice exhibited abnormal motor coordination in the rotarod test. These results indicate that GABA signaling in the cerebellum is critical for establishing appropriate connections between basket cells and Purkinje cells and is associated with motor coordination in mice.