Retinal Synaptic Transmission

描述(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动区释放。在这些神经元中，进化出了特殊的结构，称为突触带。突触带是连接活动区附近突触小泡的嗜嗅性蛋白质结构。由于它们的形态、在细胞内的位置以及它们被发现的细胞类型，这些细胞器对于谷氨酸的持续释放无疑是重要的；然而，这些细胞器如何帮助完成这一任务仍不清楚。这项拨款的重点是研究突触带在感觉突触传递中的作用，长期目标是解决与这些重要细胞释放神经递质有关的分子和细胞事件的时间序列。为此，我们使用电生理学和荧光成像相结合的方法来研究囊泡的胞吐、运输和捕获特性。具体目标1是确定带状位置和离群点位置的囊泡融合的特性。具体目标2将研究胞吐之前，丝带在收集和运输囊泡到细胞膜中所起的作用。特定目的3探索特定带状蛋白在胞吐作用中的作用。了解功能区的功能可能会提供线索，帮助理解特定影响视力和听力的疾病，如亚瑟综合征。此外，对这些特殊神经元突触前过程的基本了解将对神经元的总体交流产生更广泛的影响，从而可能有助于我们对心理健康和神经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.