Retinal Synaptic Transmission

视网膜突触传递

• 批准号: 8371335
• 负责人: DAVID Paul ZENISEK
• 金额: $ 41.53万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-08-01 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8371335
• 关键词: Action Potentials; Acute; Affect; Afferent Neurons; Auditory; Biochemical; Brain; Ca(2+)-Calmodulin Dependent Protein Kinase; Calcium; Cells; Communication; Disease; Docking; Electrophysiology (science); Event; Eye; Fluorescence; Frequencies; Funding; Glutamates; Goals; Grant; Hearing; Image; Investigation; Labyrinth; Location; Mediating; Mental Health; Molecular; Morphology; Movement; Mus; Neurons; Neurotransmitters; Organelles; Phosphorylation; Photoreceptors; Play; Process; Property; Proteins; Publishing; Recycling; Regulation; Retina; Retinal; Role; Sensory; Signal Transduction; Site; Stimulus; Structure; Synapses; Synaptic Transmission; Synaptic Vesicles; Test Result; Testing; Usher Syndrome; Vesicle; Vision; Visual; cell type; follow-up; nervous system disorder; neurotransmitter release; presynaptic; research study; response; retinal rods; ribbon synapse; tool

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. PUBLIC HEALTH RELEVANCE: In the retina and inner ear, primary sensory information is transmitted at specialized synapses, which transmit high rates of information in the form of neurotransmitter release in a graded manner. These neurons have evolved specialized structures to aid in this task and we aim to understand what these structures do for these cells. Understanding these synapses will ultimately aid in understanding how visual and auditory information is processed and communicated to the brain and will provide clues to help understand diseases that specifically affect vision and hearing.

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，这些细胞器可能是谷氨酸持续释放所必需的;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，我们使用电生理学，荧光和生物化学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研究小鼠视杆双极细胞突触的自发性和多囊泡性释放的特性，以确定突触带在协调多囊泡性释放中的作用，并探讨诱发性释放囊泡与自发性释放囊泡之间的关系。在目的2中，我们提出了调查调制的突触传递从带状突触钙钙钙调蛋白激酶ii。在目标3中，我们研究了带状物在引发囊泡持续释放神经递质中的作用。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。 公共卫生相关性：在视网膜和内耳中，初级感觉信息在专门的突触处传递，这些突触以神经递质释放的形式以分级的方式传递高速率的信息。这些神经元已经进化出专门的结构来帮助完成这项任务，我们的目标是了解这些结构对这些细胞的作用。了解这些突触最终将有助于理解视觉和听觉信息是如何处理和传达给大脑的，并将提供线索，帮助理解专门影响视觉和听觉的疾病。