Sustained transmitter release during auditory processing

听觉处理过程中持续释放递质

• 批准号: 6418662
• 负责人: LING-GANG WU
• 金额: $ 18.17万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-24 至 2006-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6418662
• 关键词: acoustic nerve; auditory nuclei; auditory pathways; brain electrical activity; calcium flux; cell population study; chelating agents; electrostimulus; hearing; laboratory rat; neural information processing; neurotransmitter metabolism; neurotransmitter transport; statistics /biometry; synapses; voltage /patch clamp

DESCRIPTION (provide by applicant) Auditory nerves may fire at high frequency for a long time upon sound stimulation. This high frequency firing is relayed with precise timing via synapses up to the auditory brainstem nuclei for sound information processing. To achieve this task, synapses must maintain transmitter release throughout the train of firing. The mechanism underlying sustained transmitter release during repetitive stimulation is not well understood at auditory synapses. I propose a new model to account for sustained transmitter release at auditory synapses. This model is composed of three hypotheses. First, sustained release during repetitive stimulation is due to both a rapid replenishment of a pool of vesicles immediately available for release (releasable pool) and a decrease in the fraction (F) of this pool being released by each impulse. The decrease in F may allow the synapse to sustain transmitter release for a longer time because it slows the rate of depletion of the releasable pool during repetitive stimulation. Secondly, the decrease in F is caused by a decrease in the affinity of the release machinery to Ca2+ Thirdly, replenishment is rapid, but independent of the stimulus intensity and Ca2+ We will test these three hypotheses with three aims, respectively, at a calyx-type synapse in the medial nucleus of the trapezoid body in the rat auditory brainstem. We will monitor membrane capacitance at the nerve terminal, which allows for more direct measurements of the releasable pool size and F. We will determine whether sustained release and relay of action potentials during high frequency firing rely on both a decrease in F and rapid replenishment of the releasable pool (Aim 1). We will increase the Ca2+ concentration by photolysis of the caged Ca2+ compound and determine whether the affinity of the release machinery to Ca2+ is decreased during repetitive stimulation (Aim 2). Finally, we will determine whether the rate of replenishment is regulated by the frequency and duration of stimulation, by the Ca2+ buffer EGTA, or by an increase in the basal Ca2+ concentration induced by photolysis of the caged Ca2+ compound (Aim 3). These studies will improve our understanding of hearing mechanisms by revealing mechanisms underlying sustained transmitter release durng repetitive firing, which is critical for conveying sound information

描述（由申请人提供）听觉神经可能以高频率放电 在声音刺激下持续很长时间。这种高频率的发射是通过 通过突触精确的计时直到听觉脑干核团 信息处理.为了完成这项任务，突触必须保持 发射器在整个发射过程中释放。的机制 在重复刺激期间持续的递质释放并不好 听觉突触的理解。我提出了一个新的模型来解释持续的 听觉突触释放的神经递质该模型由三个 假设首先，在重复刺激期间持续释放是由于 既可以迅速补充一个囊泡池， 释放（可释放池）和减少该池的分数（F）， 每一次冲动都释放出来。F的减少可能会让突触维持 发射器释放更长的时间，因为它减缓了消耗的速度， 在重复刺激过程中可释放的池。第二，F的减少 是由释放机制对Ca2+的亲和力降低引起的 第三，补充是迅速的，但与刺激强度无关， Ca2+我们将分别以三个目标来检验这三个假设， 大鼠斜方体内侧核内的萼型突触 听觉脑干我们将监测神经末梢的膜电容， 这允许更直接地测量可释放池的大小和F。我们 将决定是否持续释放和继电器的动作电位， 高频率发射既依赖于F的减少，又依赖于F的快速补充， 可释放池（目标1）。我们将通过以下方式增加Ca2+浓度： 光分解的笼状Ca2+化合物，并确定是否亲和力的 在重复刺激过程中，对Ca2+的释放机制降低（目的2）。 最后，我们将确定补货率是否受 刺激的频率和持续时间，通过Ca2+缓冲EGTA，或通过 增加基础钙离子浓度诱导的光解笼 Ca2+化合物（Aim 3）。这些研究将提高我们对听觉的理解 通过揭示持续释放递质的机制， 在重复的发射过程中，这对传达声音信息至关重要