CALCIUM-MEDIATED EXOCYTOSIS OF NEUROTRANSMITTER DURING SYNAPTIC TRANSMISSION

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 这些研究的长期目标是了解快速化学突触中递质释放的突触前机制。我们的具体目标是在三维重建的毛细胞传入突触的超微结构，以测试我们的工作模型，这个突触的功能的几个方面。毛细胞传入突触是一种带状突触，其特征是一个功能未知的电子致密细胞器，即突触体，它似乎悬浮在细胞质中活动区上方一个囊泡的宽度。透明核囊泡围绕突触体，但也存在于细胞质中，并在活性区与质膜结合。突触体的功能是什么？这些不同的囊泡池的功能意义是什么？我们将通过确定活动区和突触体的精确几何形状来解决这些问题，并绘制突触囊泡的数量和位置。通过测试这些措施的活性依赖性，我们将能够将超微结构与正在进行的生理和数学建模研究相结合，以更详细地了解导致递质胞吐的步骤。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The long-term goal of these studies is to understand the presynaptic mechanisms of transmitter release at fast chemical synapses. Our specific objective is to reconstruct in three dimensions the ultrastructure of the hair cell afferent synapse in order to test several aspects of our working model of this synapse's function. The hair cell afferent synapse is a ribbon-class synapse, characterized by an electron dense organelle of unknown function, the synaptic body, which appears to hover in the cytoplasm a vesicle's breadth above the active zone. Clear-core vesicles surround the synaptic body, but are also found in the cytoplasm, and associated with the plasma membrane at the active zone. What is the function of the synaptic body, and what is the functional significance of these various pools of vesicles? We will address these issues by determining the precise geometry of the active zone and synaptic body, and map the number and location of synaptic vesicles. By testing the activity-dependence of these measures, we will be able to integrate ultrastructure with ongoing physiological and mathematical modeling studies to build a more detailed understanding of the steps that lead to transmitter exocytosis.