Synaptic basis of motion detection in the retina

说明（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通过在其优选方向上的运动而被强烈激活，但通过在相反方向或“零”方向上的运动而被抑制。它们将运动的方向报告给更高级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，这些机制在突触水平上的实现还没有完全理解。这个提议的目的是提供对方向选择性背后的突触回路的结构-功能关系的基本见解。的 所提出的实验将集中于来自星状无长突细胞的突触输入，星状无长突细胞是共同释放GABA和乙酰胆碱到方向选择性神经节细胞上的关键中间神经元。我们将首先确定突触传递的属性和功能布线图的GABA能和胆碱能电路从星爆无长突细胞方向选择性神经节细胞，然后将确定主要的突触机制的方向选择性。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，精细分辨率光遗传学和uncaging技术来表征和操纵感兴趣的突触类型，并将突触水平机制与电路功能相关联。这项工作将提供明确的答案，悬而未决的问题，仍然是关于方向选择电路。它也将有助于了解支配感觉处理的一般原则。此外，这项研究将提供深入了解感觉系统和高级大脑结构中化学共传递的机制。

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.