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 另一种是通过突触传递。突触有效性的变化 是神经网络存储和检索信息的能力的基础， 学习和记忆的细胞表征。突触的一种形式 可塑性是一种易化现象，通过这种现象， 重复使用后更有效。便利化是一种普遍存在的现象 在许多突触中观察到，并代表了一个非常普遍的过程， 突触的有效性。这个应用程序解决了一个问题， 突触末梢内的机制使分泌增加 随着使用率的提高。 突触传递中的基本事件是钙离子进入突触膜， 突触末梢在动作电位过程中，导致一个 突触囊泡与终膜。经典的解释 易化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 小囊泡被释放。最近的研究表明， 突触囊泡被适当地激活以被释放（突触囊泡的可释放池）。 量子）是高度动态的并且在突触可塑性中具有关键作用。的 拟议工作的目标是开发和测试一个定量模型， 神经分泌，这将阐明残留的增加的作用， 钙，释放位点的激活和可释放的 量子，从而解释突触前易化。 促进有严格区分的组成部分：短期促进 (STF)和长期易化（LTF），这是由不同的基础 机制等拟议的工作将利用这些分离的优势， 两个组件来区分不同的机制。实验将 检验STF是由细胞内 钙和囊泡动员，而LTF另外由 激活先前沉默的释放位点。方法是将联合收割机 突触前过程的电生理计算机模拟 检测释放的寄生虫数量。