Synaptic basis of motion detection in the retina

视网膜运动检测的突触基础

• 批准号: 8614797
• 负责人: Wei Wei
• 金额: $ 37.44万
• 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/8614797
• 关键词: Acetylcholine; Address; Amacrine Cells; Area; Brain; Cells; Chemicals; Conscious; Data; Dendrites; Detection; Development; Electrophysiology (science); Eye Movements; Functional disorder; Genetic; Goals; Image; Interneurons; Knowledge; Label; Light; Maps; Motion; Mus; Neurons; Output; Process; Property; Public Health; Reporting; Research; Resolution; Retina; Retinal; Sensory Process; Structure; Structure-Activity Relationship; Synapses; Synaptic Transmission; Techniques; Varicosity; Vision; Visual; Visual system structure; Work; base; cell type; cholinergic; cholinergic synapse; gamma-Aminobutyric Acid; ganglion cell; innovation; insight; interest; neural circuit; optogenetics; patch clamp; postsynaptic; public health relevance; research study; response; sensory system; tool; transmission process; visual process; visual processing

Project Summary 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 for 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- and 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 the 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 knowledge 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.

项目摘要 方向选择性神经节细胞在哺乳动物视网膜中的首选中被运动强烈激活 方向，但通过相反的运动或“无效”方向抑制。他们报告了运动方向 到较高的大脑中心进行进一步的视觉处理，它们有助于控制眼动运动，并且 有意识的视力。这些神经节细胞的方向选择性归因于多个前和 突触后机制。但是，这些机制在突触级别的实施尚未完全 理解。该提案的目的是提供有关结构功能关系的基本见解 基于方向选择性的突触电路。提出的实验将集中于突触 来自Starburst Amacrine细胞的输入，这是一种关键的中间神经元，将GABA和乙酰胆碱共同释放到 方向选择性神经节细胞。我们将首先确定突触传播的特性和 从星爆肿瘤细胞到方向的GABA能和胆碱能电路的功能接线图 选择性神经节细胞，然后确定方向的主要突触机制 选择性。我们将采用一种创新的方法，将遗传细胞类型特异性靶向结合在一起， 电生理学，精细的分辨率光遗传学和分离技术来表征和操纵 突触的兴趣类型，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未悬而未决的问题提供明确的答案。会 还有助于了解管理感官处理的一般原则。而且，这 研究将洞悉感官系统中化学共传递的机理 大脑结构。