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，这些细胞器可能对谷氨酸的持续释放至关重要；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。为了做到这一点，我们使用电生理学，荧光和生化工具的组合来研究视网膜双极细胞突触传递的特性。目的1：研究小鼠棒状双极细胞突触自发和多泡释放的特性，确定条带在协调多泡释放中的作用，并研究参与诱发释放的囊泡与参与自发释放的囊泡之间的关系。在目的2中，我们建议研究钙调蛋白激酶ii对带状突触突触传递的调节。在Aim 3中，我们研究了带在启动囊泡以持续释放神经递质中的作用。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 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.