QUANTITATIVE STUDY OF PRESYNAPTIC FACILITATION

突触前促进的定量研究

• 批准号: 6651162
• 负责人: MARIA BYKHOVSKAIA
• 金额: $ 19.79万
• 依托单位: LEHIGH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-02 至 2005-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6651162
• 关键词: Malacostraca; calcium flux; computer simulation; electrophysiology; neural facilitation; neural plasticity; neural transmission; secretion; synapses

DESCRIPTION(adapted from applicant's abstract): Neurons communicate with each other through synaptic transmission. Changes in the effectiveness of synapses underlie the ability of neuronal networks to store and retrieve information, the cellular representation of learning and memory. One form of synaptic plasticity is facilitation, a phenomenon by which synapses becomes transiently more effective following repeated use. Facilitation is a ubiquitous phenomenon observed at many synapses and represents a very general process controlling the effectiveness of synapses. This application addresses the question of what mechanisms operate within the synaptic terminal to allow secretion to increase with increased rates of use. The fundamental event in synaptic transmission is the entry of calcium into the synaptic terminal during an action potential, leading to the fusion of a synaptic vesicle with the terminal membrane. The classical interpretation of facilitation was repetitive nerve stimulation increases the Ca++ concentration at presynaptic release sites, which in turn increases the probability of each vesicle to be released. Recently it was demonstrated that the number of synaptic vesicles properly activated to be released (the releasable pool of quanta) is highly dynamic and has a critical role in synaptic plasticity. The goal of the proposed work is to develop and test a quantitative model of neurosecretion, which will clarify the role of the increase in residual calcium, activation of release sites and the increase in the releasable pool of quanta and thereby account for presynaptic facilitation. Facilitation has strictly distinguishable components: short-term facilitation (STF) and long-term facilitation (LTF), which results from different underlying mechanisms. The proposed work will take advantage of the separation of these two components to distinguish between different mechanisms. Experiments will test the hypothesis that STF is determined by an increase of intracellular calcium and vesicle mobilization, while LTF is additionally controlled by activation of previously silent release sites. The approach is to combine computer simulations of presynaptic processes with electrophysiological detection of the number of released vesticles.

描述(改编自申请者的摘要)：神经元与 另一种是通过突触传递。突触有效性的变化 神经网络存储和检索信息的能力是基础， 学习和记忆的细胞表示。突触的一种形式 可塑性是一种易化现象，突触通过这种现象变得短暂 反复使用效果更佳。便利化是一种普遍存在的现象 在许多突触上观察到，并代表了一个非常一般的过程，控制 突触的有效性。这个应用程序解决的问题是 在突触终末内运行的机制允许分泌增加 随着使用率的提高。 突触传递中的基本事件是钙离子进入神经元。 在动作电位期间的突触终末，导致 与终膜相连的突触小泡。《红楼梦》的经典诠释 易化是重复神经刺激使钙离子浓度升高 在突触前释放部位，这反过来增加了每个 囊泡将被释放。最近有证据表明， 被正确激活以释放的突触小泡(可释放的池 量子)是高度动态的，在突触可塑性中起着关键作用。这个 拟议工作的目标是开发和测试一个量化模型 神经分泌，这将阐明残留增加的作用 钙，释放部位的激活和可释放池的增加 量子效应，从而解释突触前易化。 便利化有严格区分的组成部分：短期便利化 (STF)和长期促进(LTF)，这是由不同的基础导致的 机制。拟议的工作将利用这些分离的优势 用两个组件来区分不同的机制。实验将会 检验STF是由细胞内的增加决定的假设 钙和囊泡动员，而LTF另外由 激活以前沉默的释放点。其方法是将 电生理学对突触前过程的计算机模拟 检测释放的前庭数量。