CALCIUM-MEDIATED EXOCYTOSIS OF NEUROTRANSMITTER DURING SYNAPTIC TRANSMISSION

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 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。我们的具体目标是三维重建毛细胞传入突触的超微结构，以测试我们工作模型中该突触功能的几个方面。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--突触体，它似乎在细胞质中徘徊在活动区上方的一个小泡的宽度上。透明核小泡环绕突触小体，但也存在于细胞质中，并与活动区的质膜相联系。突触小体的功能是什么，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小体的精确几何形状，并绘制突触小泡的数量和位置来解决这些问题。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，以建立对导致递质胞吐的步骤的更详细的理解。

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.