Mechanisms of Synaptic Processing in the Retina

描述（由申请人提供）：本项目解决了NEI的一个基本研究重点，即了解视网膜网络如何处理视觉图像。哺乳动物视网膜包含大约20种不同类型的视网膜神经节细胞，每种细胞都有其独特的感受野特性。大多数神经节细胞类型都是图像形成的，因为它们由一组本质上完全相同的神经元组成，可以完全采样视野。我们的方法是针对特定的，解剖和生理上确定的神经节细胞，并对光诱发输入进行定量分析，以深入了解介导生理反应的神经通路的连通性。在这项建议中，我们将涉及三个目标。目的1旨在验证外丛状层AMPA和盐酸盐受体的选择性表达有助于神经节细胞的时间调节的假设。目的2旨在研究NMDA受体在方向选择性神经节细胞和ON快速持续神经节细胞产生接受野特性中的作用。我们将使用亚单位特异性拮抗剂来探测NMDA受体在ON和OFF通路中的功能差异。Aim 3与宾夕法尼亚大学的Robert Smith合作，将使用现实的计算模型来预测突触电导，并估计神经节细胞记录中电压钳误差的大小。

DESCRIPTION (provided by applicant): This project addresses a basic research priority of the NEI, which is to understand how retinal networks process visual images. The mammalian retina contains about 20 different types of retinal ganglion cell each having characteristic receptive field properties. Most ganglion cell types are image-forming in that they comprise an array of essentially identical neurons that completely sample the visual field. Our approach has been to target specific, anatomically and physiologically identified ganglion cells, and perform quantitative analyses of the light-evoked inputs in order to gain insights into the connectivity an neural pathways that mediate physiological responses. In this proposal we will address three aims. Aim 1 proposes to test the hypothesis that selective expression of AMPA and kainate receptors in the outer plexiform layer contribute to temporal tuning in the ganglion cells. Aim 2 proposes to examine the role of NMDA receptors in generating the receptive field properties of direction-selective ganglion cells, and ON brisk-sustained ganglion cells. We will use subunit-specific antagonists to probe differences in NMDA receptor function in the ON and OFF pathways. Aim 3, in collaboration with Robert Smith at University of Pennsylvania, will use realistic computational models to predict the synaptic conductances, and estimate the magnitude of voltage-clamp errors in the ganglion cell recordings. PUBLIC HEALTH RELEVANCE: The goal of this research is to understand how specific types of nerve cells in the retina transmit information about the visual scene to the brain. This information will advance our understanding of the neurobiological function of the healthy retina. The knowledge gained will help us to understand pathology in the diseased eye thus contribute to the development of therapies for human eye disease.