Synaptic basis of motion detection in the retina

视网膜运动检测的突触基础

• 批准号: 9204836
• 负责人: Wei Wei
• 金额: $ 38.94万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9204836
• 关键词: Acetylcholine; Address; Area; Brain; Cells; Chemicals; Conscious; Data; Dendrites; Detection; Development; Disease; Electrophysiology (science); Eye Movements; Functional disorder; Genetic; Goals; Image; Interneurons; Knowledge; Label; Light; Maps; Motion; Mus; Neurons; Output; Property; Public Health; Reporting; Research; Resolution; Retina; Retinal; Sensory; Structure; Structure-Activity Relationship; Synapses; Synaptic Transmission; Techniques; Varicosity; Vision; Visual; Visual system structure; Work; base; cell type; cholinergic; cholinergic synapse; directional cell; experimental study; gamma-Aminobutyric Acid; ganglion cell; innovation; insight; interest; neural circuit; optogenetics; patch clamp; postsynaptic; public health relevance; response; sensory system; starburst amacrine cell; tool; transmission process; visual processing

DESCRIPTION (provided by applicant): Direction selective ganglion cells in the mammalian retina are strongly activated by motion in their preferred direction, but are suppressed by motion in the opposite, or "null", direction. They report the direction of motion to higher brain centers or further visual processing, and they contribute to the control of eye movements and, potentially, to conscious vision. Direction selectivity of these ganglion cells is attributed to multiple pre- ad postsynaptic mechanisms. However, the implementation of these mechanisms at the synapse level is not fully understood. The goal of this proposal is to provide fundamental insights into th structure-function relationship of the synaptic circuitry that underlies direction selectivity. The proposed experiments will focus on synaptic inputs from the starburst amacrine cell, a critical interneuron that co-releases GABA and acetylcholine onto direction selective ganglion cells. We will first determine the properties of synaptic transmission and the functional wiring diagrams of the GABAergic and cholinergic circuits from starburst amacrine cells to direction selective ganglion cells, and will then identify the predominant synaptic mechanism underlying direction selectivity. We will take an innovative approach that combines genetic cell type-specific targeting, electrophysiology, fine resolution optogenetics and uncaging techniques to characterize and manipulate the synapse types of interest, and to correlate synaptic-level mechanisms with circuit function. This work will provide definitive answers to the outstanding questions that remain about the direction selective circuit. It will also contribute to the knowlede of the general principles that govern sensory processing. Moreover, this research will provide insight into the mechanism of chemical co-transmission in sensory systems and in higher brain structures.

描述（由申请人提供）：哺乳动物视网膜中的方向选择性神经节细胞被其首选方向运动强烈激活，但在相反的方向或“ null”方向上被抑制。他们向更高的大脑中心或进一步的视觉处理报告了运动方向，并有助于控制眼动运动，并有可能导致有意识的视力。这些神经节细胞的方向选择性归因于多种前突触后机制。但是，在突触水平上实施这些机制尚未完全理解。该提案的目的是提供基本的洞察力，以了解基于方向选择性的突触电路的结构功能关系。这 提出的实验将集中在Starburst Amacrine细胞中的突触输入，这是一种关键的中间神经元，将GABA和乙酰胆碱共释放到方向选择性神经节细胞上。我们将首先确定突触传播的特性以及从Starburst amacrine细胞中的GABA能和胆碱能电路的功能接线图，然后识别选择性方向选择性的主要突触机制。我们将采用一种创新的方法，该方法将遗传细胞类型特异性靶向，电生理学，精细分辨率光遗传学和分离技术结合在一起，以表征和操纵突触的感兴趣类型，并将突触级机制与电路功能相关联。这项工作将为有关方向选择性电路的杰出问题提供明确的答案。它还将有助于管理感官处理的一般原则的知识。此外，这项研究将洞悉感官系统中化学共传输的机理和更高的大脑结构。