Retinal Synaptic Transmission

描述（由申请人提供）：在眼睛和内耳的感觉神经元中，神经递质谷氨酸以分级和连续的方式在活性区释放。在这些神经元中进化出了专门的结构，称为突触带。突触带是嗜锇蛋白质结构，其将突触囊泡拴系在活动区附近。由于它们的形态，在细胞内的位置和它们被发现的细胞类型，这些细胞器无疑对谷氨酸的持续释放很重要;然而，丝带如何帮助完成这项任务仍不清楚。这项资助的重点是研究突触带在感觉突触传递中的作用，长期目标是解决参与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，我们使用电生理和荧光成像相结合的研究囊泡的胞吐，运输和捕获的性质。具体目标1是确定在带状站点和离群值位置的囊泡融合的性质。具体目标2将检查丝带在收集和转运囊泡到膜胞吐之前发挥的作用。特异性目的3探索了特异性带状蛋白在胞吐中的作用。了解丝带的功能可能会提供线索，以帮助了解疾病，特别是影响视力和听力，如Usher综合征。此外，对这些特化神经元中突触前过程的基本理解将对神经元通信产生更广泛的影响，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.