QUANTITATIVE STUDY OF PRESYNAPTIC FACILITATION

突触前促进的定量研究

• 批准号: 6196708
• 负责人: MARIA BYKHOVSKAIA
• 金额: $ 21.38万
• 依托单位: UNIVERSITY OF VIRGINIA
• 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/6196708
• 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（改编自申请人的摘要）：神经元与每个神经元进行通信 其他通过突触传递。突触有效性的变化 神经元网络存储和检索信息能力的基础， 学习和记忆的细胞表征。突触的一种形式 可塑性是一种促进作用，突触通过这种现象变得短暂 重复使用后效果更佳。便利化是一种普遍存在的现象 在许多突触处观察到，代表了控制突触的一个非常普遍的过程 突触的有效性。该应用程序解决了什么问题 突触末端内的机制使分泌增加 随着使用率的增加。 突触传递的基本事件是钙进入神经元 动作电位期间的突触末端，导致融合 具有终膜的突触小泡。经典的诠释 促进作用是重复神经刺激增加 Ca++ 浓度 在突触前释放位点，这反过来又增加了每个的概率 待释放的囊泡。最近，事实证明，数量 突触小泡被正确激活以释放（可释放池 量子）具有高度动态性，在突触可塑性中发挥着关键作用。这 拟议工作的目标是开发和测试定量模型 神经分泌，这将阐明残留增加的作用 钙，释放位点的激活和可释放池的增加 量子，从而解释突触前促进。 便利化具有严格区分的组成部分：短期便利化 （STF）和长期促进（LTF），这是由不同的潜在因素造成的 机制。拟议的工作将利用这些的分离 两个组件来区分不同的机制。实验将 检验 STF 是由细胞内的增加决定的假设 钙和囊泡动员，而 LTF 还受到以下因素的控制 激活先前静默的发布站点。该方法是结合 利用电生理学方法对突触前过程进行计算机模拟 检测释放的前泡数量。