Synaptic basis of motion detection in the retina

描述(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上的运动被强烈激活，但在相反的方向上的运动则被抑制。它们将运动的方向报告给更高的大脑中枢或进一步的视觉处理，它们有助于控制眼睛的运动，并潜在地促进有意识的视觉。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还没有完全被理解。这项建议的目的是提供对突触回路的结构-功能关系的基本见解，突触回路是方向选择性的基础。这个 拟议的实验将集中在星爆型无长突细胞的突触输入上，这是一种关键的中间神经元，共同释放GABA和乙酰胆碱到方向选择性的神经节细胞。我们将首先确定星状突触无长突细胞到方向选择性神经节细胞的突触传递特性和GABA能和胆碱能回路的功能线路图，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的方法，结合遗传细胞类型特异性靶向、电生理学、精细分辨光遗传学和去势技术来表征和操纵感兴趣的突触类型，并将突触水平的机制与电路功能联系起来。这项工作将为关于方向选择电路的悬而未决的问题提供明确的答案。它还将有助于了解管理感觉处理的一般原则。此外，这项研究将为化学共传递在感觉系统和高级大脑结构中的机制提供洞察力。

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.