Synaptic vesicle trafficking in hippocampal synapses

描述（由申请人提供）：神经元之间通信的可靠性和有效性由突触的基本特性决定。此外，突触特性的改变可能是学习和记忆形成的重要组成部分。这项研究计划的长期目标是了解突触末端释放神经递质的基本步骤，以及它们如何被调节。虽然突触前末端的许多分子已被确定，但它们在囊泡释放和再循环的各个步骤中的确切作用尚不完全清楚。突触包含功能各异的囊泡群。释放被认为是从一个被称为易释放池的小囊泡池中发生的，当这个池完全或部分耗尽时，它被来自储备池的囊泡填充。这项工作将重点描述不同的突触囊泡池，囊泡在它们之间的运动以及囊泡池特征的活动依赖性变化。实验旨在利用荧光染料和光学显微镜，结合分子生物学和电生理学，研究可视化单个突触的突触囊泡释放和运输。具体目标是确定(i)调节循环囊泡池大小和可及性的机制，（ii）外周相关突触囊泡蛋白在不同池之间的囊泡运输中的作用，以及（iii）活性依赖的囊泡池大小长期变化的机制。由于突触传递在许多神经系统疾病中受到不利影响，因此更好地了解突触释放机制将为合理的治疗提供依据。

DESCRIPTION (provided by applicant):The reliability and efficacy of communication between neurons is governed by the fundamental properties of synapses. In addition, modification of synaptic properties is likely to be a crucial component of learning and formation of memories. The long-term objectives of this research program are to understand the elementary steps in release of neurotransmitter from synaptic terminals, and how they can be modulated. Although many of the molecules in the presynaptic terminal have been identified, their precise roles in various steps in release and recycling of vesicles are incompletely understood. Synapses contain functionally heterogeneous populations of vesicles. Release is thought to occur from a small pool of vesicles termed the readily releasable pool, and when this pool is fully or partially depleted, it is filled with vesicles from the reserve pool. This work will focus on characterizing the different pool of synaptic vesicles, the movement of vesicles between them and activity-dependent changes in the characteristics of the vesicle pools. Experiments are designed to use the fluorescent dyes and optical microscopy, combined with molecular biology and electrophysiology, to study synaptic vesicle release and trafficking at visualized individual synapses. The specific objectives are to determine (i) the mechanisms regulating the size and accessibility of the recycling vesicle pool, (ii) the roles of peripherally associated synaptic vesicle proteins in trafficking of vesicles between the different pools, and (iii) the mechanisms in activity-dependent, long-term changes in the size of the vesicle pools. Since synaptic transmission is adversely affected in many disorders of the nervous system, a better understanding of synaptic release mechanisms will provide a rational basis for treatment.