MODULATION OF SYNAPTIC TRANSMISSION

每个感官系统和整个感官系统中的电信号流动 神经系统是由神经递质的分泌调节的。 分子从一个神经元到另一个神经元，或者到肌肉细胞，在 被称为突触的特殊区域。控制和调节分泌物， 或胞吐作用，以及随后突触后细胞的激活 神经系统的许多适应性和可改变的行为。二 外部刺激如何改变突触通路的显著例子 光明和黑暗深刻影响信号传输的眼睛，以及 在海马区，反复刺激神经元的输入可以 产生长时程增强或抑制突触效能。在这 建议我们将确定钙，一种重要的控制者 胞吐作用是在视杆细胞和视锥细胞中调节的。初步实验已经 表明控制锥体中的钙水平比控制杆状要快得多， 与更快的锥体响应一致。我们还将研究 多巴胺是一种神经调节物质，在 光适应，降低视杆细胞和视锥细胞中的钙水平。进一步 将进行光学直接测量胞吐作用的实验和 使用选择性染料和电生理记录从 单杆和圆锥体。在与Louis Reichardt的合作研究中，我们 将研究神经营养因子如何直接和快速地修改突触 非洲爪哇脊髓新形成的神经/肌肉突触的活动。 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 我们开发的仪器用于测量钙浓度和 突触终末的胞吐作用将被用来测量这些特征 在两种不同的制剂中的突触功能 这个项目的调查人员。所有这些研究都应该产生 对突触传递如何调节和修饰的有价值的见解 在神经系统中。

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.