Molecular Physiology--Control of Firing Properties

描述：（来自申请人摘要） 神经元在神经网络中扮演的角色是由其内在的 兴奋性，这是建立发展，以协调其 在这个网络中运行。我们将研究神经元放电的控制 大鼠外周交感神经系统的特性。有两 这个系统中的神经元类型。椎旁神经节中的神经元具有简单的 这些细胞的连接图和突触输入由一个大的 来自单个节前运动神经元的阈上输入。这些细胞 响应于持续去极化电流而被强烈地调节， 称为相位神经元。相反，椎前神经节中的神经元整合 来自感觉和运动神经元的多个小突触输入。这些细胞 响应于持续的去极化电流而重复地激发 作为紧张性神经元。 这些不同的烧成特性是由微分表达式决定的 特定的钾电流。相性放电是由一种 相对较大的M电流。紧张性放电特性与表达相关 一个内向整流电流和一个低阈值， 称为D2电流。这两种不同的电生理表型是 在发育过程中由影响转录的诱导事件决定 钾通道基因的调控。 该提案的总体目标是确定以下物质的分子身份： 这些电流控制着点火特性的开关， 这些渠道是如何实现的。这项工作与 癫痫的研究，因为内在神经元兴奋性的调节 是决定神经网络整体兴奋性的关键因素。

DESCRIPTION:(from applicant's abstract) The role that a neuron plays in a neural network is shaped by its intrinsic excitability, which is established developmentally to co-ordinate with its function within that network. We will study the control of neuronal firing properties in the rat peripheral sympathetic nervous system. There are two types of neurons in this system. Neurons in paravertebral ganglia have a simple wiring diagram and synaptic input to these cells is dominated by a large suprathreshold input from a single preganglionic motor neuron. These cells strongly accommodate in response to a sustained depolarizing current and are known as phasic neurons. In contrast, neurons in prevertebral ganglia integrate multiple small synaptic inputs from both sensory and motor neurons. These cells fire repetitively in response to a sustained depolarizing current and are known as tonic neurons. These different firing properties are determined by the differential expression of specific potassium currents. Phasic firing is produced by expression of a relatively large M-current. Tonic firing properties correlate with expression of an inward rectifier current and a low threshold, slowly inactivating current known as a D2 current. These two distinct electrophysiological phenotypes are determined during development by inductive events that affect transcriptional regulation of potassium channel genes. The overall aim of this proposal is to determine the molecular identity of those currents that control the switch in firing properties and to understand how the regulation of these channels is achieved. This work has relevance to the study of epilepsy since the regulation of intrinsic neuronal excitability is a key factor in determining the overall excitability of a neural network.