Molecular Physiology--Control of Firing Properties

描述：(摘自申请人的摘要) 神经元在神经网络中扮演的角色是由其内在的 兴奋性，这是在发育过程中建立的，以与其 在该网络中运行。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。有两个 这个系统中的神经元的类型。椎旁神经节中的神经元有一个简单的 这些细胞的接线图和突触输入是由一个大的 来自单个节前运动神经元的超阈值输入。这些细胞 强烈适应持续的去极化电流，并且是 被称为时相神经元。相反，椎前神经节中的神经元整合 来自感觉神经元和运动神经元的多个小突触输入。这些细胞 响应持续的去极化电流而重复发射，已知 作为紧张性神经元。 这些不同的激发属性由差分表达式确定 特定的钾电流。阶段性激发是通过表达一个 相对较大的动静电流。强直的激发特性与表情相关 内向整流电流和低阈值缓慢失活电流 被称为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的 钾通道基因的调控。 这项提议的总体目标是确定分子身份 这些电流控制着开关的触发特性，并了解 如何实现对这些渠道的监管。这项工作与 神经内源性兴奋性调控对癫痫的研究进展 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.