Retinal Synaptic Transmission

视网膜突触传递

基本信息

批准号：
8913185
负责人：
DAVID Paul ZENISEK
金额：
$ 52.08万
依托单位：
YALE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2003
资助国家：
美国
起止时间：
2003-08-01 至 2017-08-31
项目状态：
已结题

项目摘要

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.

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域释放。这些神经元中进化出了特殊的结构，称为突触带。突触带是嗜锇蛋白质结构，将突触小泡束缚在活动区域附近。由于它们的形态、在细胞内的位置以及它们所在的细胞类型，这些细胞器可能对于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仍不清楚。该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顺序。为此，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突触传递的特性。目的 1 是研究小鼠杆状双极细胞突触自发和多囊泡释放的特性，以确定丝带在协调多囊泡释放中的作用，并研究参与诱发释放的囊泡和参与自发释放的囊泡之间的关系发布。在目标 2 中，我们建议研究钙钙调蛋白激酶 ii 对带状突触突触传递的调节。在目标 3 中，我们研究了丝带在启动囊泡以持续释放神经递质中的作用。了解丝带功能可能提供线索，帮助了解特别影响视力和听力的疾病，例如亚瑟综合症。此外，对这些特殊神经元突触前过程的基本理解将对一般神经元通讯产生更广泛的影响，因此可能有助于我们对心理健康和神经系统疾病各个方面的理解。

项目成果

期刊论文数量（9）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Vesicle association and exocytosis at ribbon and extraribbon sites in retinal bipolar cell presynaptic terminals.

视网膜双极细胞突触前末梢丝带和丝带外位点的囊泡关联和胞吐作用。

DOI：
10.1073/pnas.0709067105
发表时间：
2008
期刊：
Proceedings of the National Academy of Sciences of the United States of America
影响因子：
11.1
作者：
Zenisek,David
通讯作者：
Zenisek,David

Vesicle reuse revisited.

重新审视囊泡的再利用。

DOI：
10.1073/pnas.0502910102
发表时间：
2005
期刊：
Proceedings of the National Academy of Sciences of the United States of America.
影响因子：
0
作者：
Zenisek,David
通讯作者：
Zenisek,David

Imaging exocytosis in retinal bipolar cells with TIRF microscopy.