MODULATION OF SYNAPTIC TRANSMISSION

突触传递的调节

• 批准号: 6205000
• 负责人: DAVID Richard COPENHAGEN
• 金额: $ 14.82万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-01 至 2000-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6205000
• 关键词: Urodela; Xenopus; calcium flux; cone cell; dopamine; exocytosis; in situ hybridization; laboratory mouse; neural conduction; neural information processing; neural transmission; neuroregulation; retinal adaptation; rod cell; synaptogenesis; visual phototransduction; voltage /patch clamp

The flow of electrical signals in every sensory system and throughout the nervous system is mediated by the secretion of neurotransmitter molecules from one neuron to another neuron, or to a muscle cell, at specialized regions called synapses. Control and regulation of secretion, or exocytosis, and subsequent activation of postsynaptic cells underlies much of the adaptive and modifiable behavior of the nervous system. Two striking examples of how external stimuli modify synaptic pathways are in the eye where light and dark profoundly influence signal transmission and in the hippocampus where repeated stimulation of inputs to a neuron can produce long term potentiation or depression of synaptic efficacy. In this proposal we will determine how calcium, an important controller of exocytosis, is regulated in rods and cones. Preliminary experiments have shown that control of calcium levels in cones is much faster than rods, consistent with the much faster cone responses. We will also examine the mechanism by which dopamine, a neuromodulator substance that rises during light-adaptation, reduces calcium levels in both rods and cones. Further experiments will be done to directly measure exocytosis optically and electrically using selective dyes and electrophysiological recordings from single rods and cones. In a collaborative study with Louis Reichardt, we will investigate how neurotrophins directly and quickly modify synaptic activity at newly formed nerve/muscle synapses from Xenopus spinal cord. We will determine the intracellular pathways and important molecular structures of the signalling molecules. Additionally, the techniques and instrumentation we have developed to measure calcium concentrations and exocytosis in synaptic terminals will be applied to measure these features of synaptic function in two different preparations used by two other investigators on this program project. All of these studies should yield valuable insights into how synaptic transmission is regulated and modified in the nervous system.

电信号在每个感觉系统中的流动 神经系统由神经递质的分泌介导 分子从一个神经元到另一个神经元，或到肌肉细胞， 称为突触的特殊区域。控制和调节分泌， 或胞吐作用，随后激活突触后细胞， 神经系统的许多适应性和可修改的行为。两 外部刺激如何改变突触通路的突出例子是， 光和暗深刻影响信号传输的眼睛， 在海马体中，对神经元输入的重复刺激可以 产生突触功效的长期增强或抑制。在这 建议我们将确定如何钙，一个重要的控制器， 胞吐作用在视杆细胞和视锥细胞中受到调节。初步实验已经 表明视锥细胞对钙水平的控制比视杆细胞快得多， 与更快的视锥细胞反应一致。我们亦会研究 多巴胺是一种神经调节物质， 光适应，降低视杆细胞和视锥细胞中的钙水平。进一步 将进行实验以光学地直接测量胞吐作用， 电使用选择性染料和电生理记录， 单个的视杆细胞和视锥细胞在与Louis Reichardt的一项合作研究中， 将研究神经营养因子如何直接和快速地改变突触 活动在新形成的神经/肌肉突触从爪蟾脊髓。 我们将确定细胞内途径和重要分子 信号分子的结构。此外，技术和 我们已经开发了测量钙浓度的仪器， 将应用突触末梢中的胞吐作用来测量这些特征 突触功能的两个不同的准备工作， 这个项目的调查员。所有这些研究应该会产生 突触传递是如何被调节和修饰的 在神经系统中。