REGULATION OF TRANSMITTER RELEASE AT CENTRAL SYNAPSES

突触功能障碍是情感、学习、 记忆和运动控制。建议的长期目标是 研究是为了了解发射器释放的规则在 中枢突触，这是神经元的基本元素 通信，并为许多底层机制提供基础 神经网络的自适应特性。的函数关联性 胞吐作用的量子模型，它允许识别 突触的可塑性仍然存在争议，特别是决定因素 释放的随机性。第一个目标是为了测试 与结构相关的特定假设的有效范围 并在单个突触单位起作用，即假设 动作电位触发每个细胞最多释放一个囊泡 突触前活动区。相应地，量子单位的数量 通过对响应波动的统计分析确定的不应 超过组成突触连接的活动区的数量。 对诱发反应的统计分析将与 两种制备方法中突触连接的超微结构数据：I) 金鱼突触前突触之间的兴奋性联系 Mauthner(M-)轴突与颅脑中继突触后轴突 神经元(CRN)，以及II)体细胞上的单抑制突触 培养大鼠延髓和脊髓神经元。细胞外钙离子 将有所不同，以允许不同的基线水平的释放。第二 目的是检验这样一个假设，即自发或微型量子 单位不一定是刺激诱发的构件 反应，但确实提供了关于囊泡周期和 释放动力学。具体的问题是量子大小是否更小 在M轴突至CRN的突触抑制过程中 连接以及诱发的反应是否扭曲了衰减时间 其分布可与迷你行星相媲美。或者，慢慢来 迷你意味着单个囊泡的释放速度比 动作潜力？最后一个目标是检验抑郁症的假设 在M轴突到CRN的连接不是由于简单的 可用的囊泡池，但却是突触前钙离子内流 触发两个相互竞争的进程，同步释放和瞬时 抑郁症。为此，对频率依赖的量子分析 和配对的脉搏抑制将与手法相结合 释放，如突触前注射钙离子，特定的激酶， 抗体和多肽。来自所有AIMS的结果将允许更多 关于发射机分子机制的统一而连贯的观点 释放及其不确定性。

Synaptic dysfunction is the basis of disorders of affect, learning, memory and motor control. The long-term goal of the proposed research is to understand the regulation of transmitter release at central synapses, which are the fundamental elements of neuronal communication and provide the basis for many mechanisms underlying adaptive properties of neuronal networks. Functional correlates of the quantal model of exocytosis, which allows identification of loci of synaptic plasticity remain controversial, in particular, the determinants of the stochastic nature of release. The first aim is designed to test the range of validity of a specific hypothesis that correlates structure and function at single synaptic units, namely the hypothesis that an action potential triggers the release of at most one vesicle per presynaptic active zone. Accordingly, the number of quantal units determined by statistical analysis of response fluctuations should not exceed the number of active zones comprising a synaptic connection. Statistical analyses of evoked responses will be combined with ultrastructural data on synaptic connectivity in two preparations: I) identified excitatory connections in goldfish between the presynaptic Mauthner (M-) axon and the postsynaptic axon of cranial relay neurons (CRNs), and ii) single inhibitory eynapses on somata of cultured rat medullary and spinal cord neurons. Extracellular Ca++ will be varied, to allow different baseline levels of release. The second aim is to test the hypothesis that the spontaneous or miniature quantal unit is not necessarily the building block of the stimulus evoked response but does provide insight concerning the vesicle cycle and the kinetics of release. Specific issues are whether quantal size is smaller than minis during synaptic depression at the M-axon to CRN connection and whether evoked responses have skewed decay time distributions comparable to those of minis. Alternatively, do slow minis signify a slower release of single vesicles than occurs after an action potential? The last aim is to test the hypothesis that depression at the M-axon to CRN connection is not due to a simple depletion of the available vesicle pool but that instead a presynaptic Ca++ influx triggers two competing processes, synchronous release and transient depression. For this purpose, quantal analysis of frequency dependent and paired pulse depression will be combined with manipulations of release, such as presynaptic injections of Ca++, specific kinases, antibodies and peptides. The results form all aims will allow a more unified and coherent view of the molecular mechanisms of transmitter release and its uncertainty.