Inferior Olivary TMEM16B Mediates Cerebellar Motor Learning.,Neuron

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Inferior Olivary TMEM16B Mediates Cerebellar Motor Learning.
Neuron ( IF 14.7 ) Pub Date : 2017-Aug-30 , DOI: 10.1016/j.neuron.2017.08.010
Yang Zhang ₁ , Zhushan Zhang ₁ , Shaohua Xiao ₂ , Jason Tien ₂ , Son Le ₁ , Trieu Le ₁ , Lily Y Jan ₂ , Huanghe Yang ₃

Affiliation

Ca²⁺-activated ion channels shape membrane excitability and Ca²⁺ dynamics in response to cytoplasmic Ca²⁺ elevation. Compared to the Ca²⁺-activated K⁺ channels, known as BK and SK channels, the physiological importance of Ca²⁺-activated Cl^- channels (CaCCs) in neurons has been largely overlooked. Here we report that CaCCs coexist with BK and SK channels in inferior olivary (IO) neurons that send climbing fibers to innervate cerebellar Purkinje cells for the control of motor learning and timing. Ca²⁺ influx through the dendritic high-threshold voltage-gated Ca²⁺ channels activates CaCCs, which contribute to membrane repolarization of IO neurons. Loss of TMEM16B expression resulted in the absence of CaCCs in IO neurons, leading to markedly diminished action potential firing of IO neurons in TMEM16B knockout mice. Moreover, these mutant mice exhibited severe cerebellar motor learning deficits. Our findings thus advance the understanding of the neurophysiology of CaCCs and the ionic basis of IO neuron excitability.

中文翻译：

下橄榄 TMEM16B 介导小脑运动学习。

Ca ²⁺激活的离子通道对细胞质 Ca ²⁺升高作出反应，形成膜的兴奋性和 Ca ²⁺动力学。与被称为 BK 和 SK 通道的 Ca ²⁺激活的 K ^{+通道相比，Ca}²⁺激活的 Cl ^-通道 (CaCCs) 在神经元中的生理重要性在很大程度上被忽视了。在这里，我们报告 CaCC 与下橄榄 (IO) 神经元中的 BK 和 SK 通道共存，这些通道发送攀爬纤维来支配小脑浦肯野细胞，以控制运动学习和时间。Ca ²⁺通过树枝状高阈值电压门控 Ca ^2+流入通道激活 CaCC，这有助于 IO 神经元的膜复极化。TMEM16B 表达的丧失导致 IO 神经元中缺乏 CaCC，导致 TMEM16B 敲除小鼠中 IO 神经元的动作电位放电显着降低。此外，这些突变小鼠表现出严重的小脑运动学习缺陷。因此，我们的研究结果促进了对 CaCC 的神经生理学和 IO 神经元兴奋性的离子基础的理解。

更新日期：2017-08-31

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