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被沿其偏好方向的运动强烈激活，但被沿相反方向或“无效”方向的运动抑制。它们向更高的大脑中心或进一步的视觉处理报告运动方向，并且有助于控制眼球运动，并可能有助于有意识的视觉。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，这些机制在突触层面的实现尚不完全清楚。该提案的目标是提供对作为方向选择性基础的突触电路的结构-功能关系的基本见解。的 拟议的实验将重点关注星爆无长突细胞的突触输入，星爆无长突细胞是一种关键的中间神经元，可将 GABA 和乙酰胆碱共同释放到方向选择性神经节细胞上。我们将首先确定突触传递的特性以及从星爆无长突细胞到方向选择性神经节细胞的 GABA 能和胆碱能回路的功能接线图，然后确定方向选择性背后的主要突触机制。我们将采取一种创新方法，结合遗传细胞类型特异性靶向、电生理学、高分辨率光遗传学和解笼锁技术来表征和操纵感兴趣的突触类型，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电路的悬而未决的问题提供明确的答案。它还将有助于了解控制感觉处理的一般原理。此外，这项研究还将深入了解感觉系统和高级大脑结构中化学协同传递的机制。

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.