MODULATION OF SYNAPTIC TRANSMISSION

突触传递的调节

• 批准号: 6495431
• 负责人: DAVID Richard COPENHAGEN
• 金额: $ 22.55万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-01 至 2002-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6495431
• 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.

每个感觉系统和整个感觉中电信号的流动 神经系统由神经递质的分泌介导 从一个神经元到另一个神经元或肌肉细胞的分子在 专门的区域称为突触。控制和调节分泌， 或胞吐作用以及后突触后细胞的激活 神经系统的许多适应性和可修改行为。二 外部刺激如何修改突触途径的惊人示例 光线和深色深刻影响信号传递和的眼睛 在海马中，反复刺激对神经元的输入可以 产生长期增强或突触功效的抑郁症。在这个 提案我们将确定钙如何，一个重要的控制器 胞吐作用，在杆和锥体中调节。初步实验具有 表明，锥体中钙水平的控制速度比杆更快， 与更快的圆锥响应一致。我们还将检查 多巴胺（一种神经调节剂物质）在此期间上升的机制 光适应，降低了杆和锥的钙水平。更远 将进行实验，以直接从光学上测量胞吐作用和 使用选择性染料和电生理记录 单杆和锥体。在与路易斯·雷卡特（Louis Reichardt）的合作研究中，我们 将研究神经营养蛋白如何直接，快速修饰突触 在新形成的神经/肌肉突触中的活性来自爪蟾脊髓。 我们将确定细胞内途径和重要的分子 信号分子的结构。此外，这些技术和 我们已经开发了仪器来测量钙浓度和 突触终端中的胞吐作用将用于测量这些特征 在另外两个不同的两种不同制剂中的突触功能 该计划项目的调查人员。所有这些研究都应产生 关于如何调节和修改突触传播的宝贵见解 在神经系统中。