Synaptic basis of motion detection in the retina

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在其首选方向的运动中被强烈激活，但在相反或“无效”方向的运动中被抑制。它们将运动的方向报告给更高的大脑中心或进一步的视觉处理，它们有助于控制眼球运动，并有可能控制有意识的视觉。这些神经节细胞的方向选择性归因于多种突触前和突触后机制。然而，这些机制在突触水平上的实现并不完全清楚。这一建议的目标是提供基本的见解突触电路的结构-功能关系的基础上的方向选择性。这个

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.