CELLULAR MECHANISMS OF INFORMATION PROCESSING IN NEURONS

描述 这项拟议研究的总体目标是了解细胞 单个神经元处理信息的基础机制。一个 这一过程中的关键一步是将膜电位转化为 动作电位。最近对锥体神经元的研究表明，由于一种 低阈值，动作电位的起始发生在轴突。什么 然而，确定这一阈值的方法尚不清楚。第一个假设 有待检验的是，动作电位启动的阈值较低 在轴突中比在胞体中更多，因为Na+通道密度高， 轴突内A型通道密度较低。具体目标是1) 测定和比较相对密度和生物物理参数 用膜片钳技术研究轴突和胞体的Na+和K+通道 2)确定哪些渠道是阈值的主要决定因素 在全细胞过程中药理调节阈值的轴突 正在录音。第二个假设是，在最初的时候，抑制性突触 节段通过将电流减少到 轴突的起始点。具体的目标是确定 胞体和轴突之间的电压降和用来测量阈值 并且没有激活起始片段上的GABAA受体，以及4)到 确定动作电位起始点是否向树突转移 当阈值通过激活GABAA受体而提高时 Segment和Soma。这些研究将提供亟需的数据 动作电位启动的细胞机制及其机制 调制。

DESCRIPTION The overall goal of the proposed research is to understand the cellular mechanisms that underlie the processing of information by single neurons. A key step in this processing is the conversion of membrane potential into action potentials. Recent work in pyramidal neurons suggests that, due to a low threshold, initiation of action potentials occurs in the axon. What determines this threshold, however, is not understood. The first hypothesis to be tested is that the threshold for action potential initiation is lower in the axon than in the soma because the density of Na+ channels is high and the density of A-type channels is low in the axon. The Specific Aims are 1) To determine and compare the relative densities and biophysical parameters of Na+ and K+ channels in the axon and soma using patch-clamp techniques and 2) to determine which channels are major determinants of threshold in the axon by manipulating threshold pharmacologically during whole-cell recording. The second hypothesis is that inhibitory synapses on the initial segment increase action potential threshold by decreasing current flow to the site of initiation in the axon. The Specific Aims are to 3) determine the voltage drop between the soma and axon and to measure thresholds with and without activation of GABAA receptors on the initial segment, and 4) to determine if the site of action potential initiation shifts to the dendrites when the threshold is raised by activation of GABAA receptors on the initial segment and soma. These studies will provide much needed data on the cellular mechanisms underlying action potential initiation and its modulation.