Retinal Synaptic Transmission

描述（由申请人提供）：在眼睛和内耳的感觉神经元中，神经递质谷氨酸在活跃区以分级和连续的方式释放。在这些神经元中进化出了称为突触带的特殊结构。突触带是一种亲锇的蛋白质结构，它将突触囊泡系在活性区附近。由于它们的形态、在细胞内的位置和发现它们的细胞类型，这些细胞器对谷氨酸的持续释放无疑是重要的；然而，丝带如何帮助完成这项任务尚不清楚。这项资助的重点是研究突触带在感觉突触传递中的作用，长期目标是解决涉及这些重要细胞释放神经递质的分子和细胞事件的时间序列。为此，我们采用电生理学和荧光成像相结合的方法来研究囊泡胞吐、转运和捕获的特性。具体目的1是确定囊泡融合在带状位点和离群位点的性质。特异性目的2将检查在胞吐前，带在收集和运输囊泡到膜中的作用。特异性目的3探讨特异性带蛋白在胞吐作用中的作用。了解脑带的功能可能会提供一些线索，帮助我们了解一些特别影响视力和听力的疾病，比如Usher综合征。此外，对这些特殊神经元突触前过程的基本理解将对一般的神经元交流产生更广泛的影响，因此，可能有助于我们对精神健康和神经系统疾病的各个方面的理解。

DESCRIPTION (provided by applicant): In sensory neurons of the eye and inner ear the neurotransmitter, glutamate, is released at active zones in a graded and continuous manner. In these neurons specialized structures have evolved, known as synaptic ribbons. Synaptic ribbons are osmiophilic proteinaceous structures that tether synaptic vesicles near active zones. Because of their morphology, location within the cells and the cell types where they are found, these organelles are undoubtedly important for the continuous release of glutamate; how ribbons aid in this task, however, remains unclear. The focus of this grant is to study the role of synaptic ribbons in sensory synaptic transmission, with the long term goal to resolve the temporal sequence of molecular and cellular events that are involved in the release of neurotransmitter from these important cells. To do this we use combination of electrophysiology and fluorescence imaging to study the properties of vesicle exocytosis, transport and capture. Specific Aim 1 is to determine the properties of vesicle fusion at ribbon sites and outlier locations. Specific Aim 2 will examine the role the ribbon plays in collecting and transporting vesicles to the membrane prior to exocytosis. Specific Aim 3 explores the role of specific ribbon proteins in exocytosis. Understanding ribbon function may provide clues to help understand diseases that specifically affect vision and hearing, such as Usher syndrome. In addition, the fundamental understanding of presynaptic processes in these specialized neurons will have broader implications for neuronal communication in general and thus, may contribute to our understanding of various aspects of mental health and neurological disorders.