Mechanisms of Synaptic Processing in the Retina

描述(由申请人提供)：该项目致力于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。哺乳动物的视网膜包含大约20种不同类型的视网膜神经节细胞，每种细胞都具有独特的感受野特性。大多数神经节细胞类型都是成像细胞，因为它们由一系列基本上相同的神经元组成，完全采样视野。我们的方法是以特定的、解剖学和生理学识别的神经节细胞为目标，对光诱发的输入进行定量分析，以便深入了解参与生理反应的神经通路的连通性。在这项提案中，我们将解决三个目标。目的1验证外丛状层AMPA和海人藻酸受体选择性表达有助于神经节细胞时间调谐的假说。目的2研究NMDA受体在方向选择性神经节细胞和快感神经节细胞产生感受野特性中的作用。我们将使用亚基特异性拮抗剂来探索NMDA受体在开和关通路中的功能差异。Aim 3与宾夕法尼亚大学的罗伯特·史密斯合作，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幅度。 与公共健康相关：这项研究的目标是了解视网膜中特定类型的神经细胞如何将有关视觉场景的信息传输到大脑。这些信息将促进我们对健康视网膜的神经生物学功能的理解。所获得的知识将有助于我们了解眼部疾病的病理，从而有助于人类眼病治疗方法的发展。

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.