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，以分级且连续的方式在活动区域​​释放。在这些神经元中，专业结构已经发展，称为突触带。突触丝带是渗透性蛋白质结构，它们在活性区域附近绑定突触囊泡。由于它们的形态，在细胞及其发现的细胞类型中的位置，这些细胞器可能对于连续释放谷氨酸可能是必不可少的。然而，丝带如何辅助这项任务尚不清楚。该赠款的重点是研究突触色带在感觉突触传播中的作用，其长期目标是解决从这些重要细胞中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，荧光和生化工具的组合来研究视网膜双极细胞突触传播的特性。 AIM 1是研究从小鼠杆杆双极细胞突触中自发和多动物释放的特性，以确定色带在协调多氧化释放中的作用，并研究涉及诱发释放的囊泡和参与自发释放的囊泡之间的关系。在AIM 2中，我们建议研究通过钙钙调蛋白激酶II从色带突触传播的突触传播。在AIM 3中，我们研究了色带在连续神经递质释放的启动囊泡中的作用。了解色带功能可能会提供线索，以帮助理解特别影响视力和听力的疾病，例如Usher综合征。此外，对这些专业神经元中突触前过程的基本理解将对一般的神经元交流具有更广泛的影响，因此，可能有助于我们对心理健康和神经系统疾病的各个方面的理解。 公共卫生相关性：在视网膜和内耳中，主要的感官信息以专门的突触传输，该突触以神经递质释放的形式传输高信息速率，以分级的方式传输。这些神经元发展了专门的结构以帮助完成这项任务，我们旨在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如何处理和传达给大脑的视觉和听觉信息，并将提供线索，以帮助理解特别影响视力和听力的疾病。