Structure and Function of Primate Retinal Circuits

灵长类动物视网膜回路的结构和功能

基本信息

批准号：
10318653
负责人：
Teresa Puthussery
金额：
$ 37.77万
依托单位：
UNIVERSITY OF CALIFORNIA BERKELEY
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-01-01 至 2024-11-30
项目状态：
已结题

项目摘要

An understanding of the normal structure and function of the retina is important to appreciate changes that occur during disease, development and aging. To this end, a longstanding goal for the field has been to obtain a unified functional, molecular and morphological classification of the neural cell types in the primate retina. To address this need, we will use a state-of-the-art approach to interrogate neuronal function in molecularly-defined ganglion and amacrine cell types in primate retina. Our method combines two-photon calcium imaging of light-evoked responses with a novel, high-throughput method to molecularly classify cell types in situ and at unprecedented scale. We will use this integrated approach to determine the functional properties of molecularly-defined wide-field ganglion cells and GABAergic amacrine cell types that have hitherto been difficult to target using conventional electrophysiological approaches. In Aim 1, we will determine the spatiotemporal response properties, mosaics and morphologies of ganglion cell types that are disproportionately represented in peripheral retina. In Aim 2, we will examine how regional differences in inhibitory neurons and their connections shape the functional response properties of the foveal and peripheral retina. We expect that completion of these aims will reveal novel insights into the distinct cellular and circuit mechanisms that shape visual processing in the foveal and peripheral retina.

了解视网膜的正常结构和功能对于理解变化很重要发生在疾病、发育和衰老过程中。为此，该领域的长期目标是获得神经细胞类型的统一功能、分子和形态学分类灵长类动物的视网膜。为了满足这一需求，我们将使用最先进的方法来询问神经元在灵长类视网膜中分子定义的神经节和无长突细胞类型中发挥作用。我们的方法将光诱发反应的双光子钙成像与一种新颖的高通量方法相结合以前所未有的规模对细胞类型进行原位分子分类。我们将使用这个集成的确定分子定义的广域神经节细胞功能特性的方法和 GABA 能无长突细胞类型迄今为止难以使用常规方法靶向电生理学方法。在目标 1 中，我们将确定时空响应属性，神经节细胞类型的马赛克和形态在外周细胞中比例不成比例视网膜。在目标 2 中，我们将研究抑制性神经元及其连接的区域差异如何塑造中心凹和周边视网膜的功能反应特性。我们预计完成这些目标将揭示对塑造不同细胞和电路机制的新见解中央凹和周边视网膜的视觉处理。