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，这些细胞器可能是持续释放谷氨酸所必需的；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。为了做到这一点，我们结合使用电生理学、荧光和生化工具来研究视网膜双极细胞的突触传递特性。目的1研究小鼠杆状双极细胞突触自发释放和多泡释放的特性，以确定条带在协调多泡释放中的作用，并探讨参与诱发释放的小泡与参与自发释放的小泡之间的关系。在目标2中，我们建议研究钙调素蛋白激酶II对带状突触突触传递的调节作用。在目标3中，我们研究了丝带在启动囊泡持续神经递质释放中的作用。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 likely essential 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 a combination of electrophysiology, fluorescence and biochemical tools to study the properties of synaptic transmission from retinal bipolar cells. Aim 1 is to investigation the properties of spontaneous and multi-vesicular release from the mouse rod bipolar cell synapse to determine the role of the ribbon in coordinating multi-vesicular release and to investigate the relationship between vesicles involve in evoked release and those involved in spontaneous release. In Aim 2, we propose to investigate modulation of synaptic transmission from ribbon synapses by calcium calmodulin kinase ii. In Aim 3, we investigate the role of the ribbon in priming vesicles for continuous neurotransmitter release. 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.