K+ channels in fast-spiking cell synaptic transmission

描述(由申请人提供)： 癫痫影响着世界1%-2%的人口。鉴于电压门控离子通道在神经元兴奋性调节中的作用，人们普遍认为离子通道参与了至少某些形式的本病的发病机制。事实上，各种类型的癫痫都是由于编码选择性钾(K+)的电压门控通道成分的基因突变所致。电压门控K+通道Kv3.1和Kv3.2缺陷的小鼠是癫痫，可能是由于皮质抑制受损。本项目旨在利用小鼠大脑皮层双全细胞膜片钳记录，研究KV3.1/Kv3.2在快峰GABA能中间神经元(FS细胞)特性中的作用。特别感兴趣的是Kv3.1和Kv3.2在(1)FS细胞终末的神经传递中的作用，以及(2)相互连接的FS细胞的网络行为。该项目将探索KV3.1/3.2基因敲除小鼠FS细胞终末GABA释放的动力学及其错乱，以及这些小鼠同步FS细胞行为的中断。这项工作可能会对正常的认知功能以及涉及GABA能系统的神经病理学产生影响，包括癫痫。

DESCRIPTION (provided by applicant): Epilepsy affects 1-2% of the world's population. Given the role of voltage-gated ion channels in the regulation of neuronal excitability, there is general agreement that ion channels are involved in the pathogenesis of at least some forms of this disease. In fact, various types of epilepsy are due to mutation of genes that encode for components of voltage-gated channels selective for potassium (K+). Mice defective in the voltage-gated K+ channels Kv3.1 and Kv3.2 are epileptic, likely due to impaired cortical inhibition. This project seeks to study the role of Kv3.1/Kv3.2 in the properties of fast-spiking GABAergic interneurons (FS cells) - where these channels are specifically expressed - using dual whole-cell patch clamp recordings in the neocortex of mouse. Of particular interest are the roles of Kv3.1 and Kv3.2 in (1) neurotransmission at the FS cell terminal, and (2) the network behavior of interconnected FS cells. This project will explore the dynamics of GABA release at the FS cell terminal and its derangement in Kv3.1/3.2 knockout mice, and the disruption of synchronous FS cell behavior in these mice. This work may have implications for normal cognitive functions as well as neuropathology involving the GABAergic system, including epilepsy.