MECHANISMS OF TEMPORAL ENCODING IN RETINAL BIPOLAR CELLS

视网膜双极细胞的时间编码机制

• 批准号: 8106973
• 负责人: Tomomi Ichinose
• 金额: $ 33.67万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-01 至 2012-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8106973
• 关键词: Address; Biological Neural Networks; Cations; Cells; Code; Color; Complex; Eye; Future; Glutamate Receptor; Goals; Kinetics; Light; Link; Molecular; Molecular Genetics; Nature; Neurons; Pathway interactions; Patients; Physiological; Process; Research; Retina; Retinal; Retinal Ganglion Cells; Shapes; Signal Transduction; Speed; Synapses; Testing; Time; Vision; Visual; Visual system structure; Work; base; computerized data processing; design; ganglion cell; gene therapy; improved; parallel processing; relating to nervous system; response; retinal prosthesis; therapy development; visual information; voltage; voltage gated channel

DESCRIPTION (provided by applicant): Our visual system perceives the world as functions of time, space, and color. The time (temporal) information, defining the speed of an object ranging from fast moving to stationary, is encoded in temporal processing pathways in the visual system. These pathways are broadly classified into transient pathways and sustained pathways based on their neural responses. The former encodes fast changing visual information, whereas the latter encodes static information. Earlier work suggested that these different temporal processing pathways occurred in retinal ganglion cells. Two morphologically different ganglion cells (a- and ¿-ganglion cells) were the origin for these two distinct functional pathways. Recent studies have suggested that retinal bipolar cells, which are upstream of ganglion cells, are critical for the parallel processing of visual information. Morphological studies have revealed more than 10 subtypes of bipolar cells in the mammalian retina, which might initiate distinct pathways encoding different features of temporal signals. To date, no studies have addressed how each subtype of bipolar cell in the mammalian retina encodes temporal visual information. In response to this research gap, my goal is to understand the cellular and molecular mechanisms of temporal encoding in each subtype of ON bipolar cell. In the proposed study, I will investigate how each subtype of ON bipolar cell encodes distinct temporal visual information in the mammalian retina. First, I will examine physiological aspects of temporal encoding in each subtype of ON bipolar cell (Aim 1). Next, I will examine the possible molecular mechanisms of temporal encoding: intracellular Ca++ increase evoked by mGluR6 signaling (Aim 2), and voltage-gated channels (Aim 3). It has become increasingly difficult to ignore the need for a functional retinal prosthesis and molecular genetics approaches to restore vision for diseased eyes. The proposed study will improve our understanding of parallel processing in the retinal network, which will contribute to the future design of a functional retinal prosthesis and sight restoring gene therapies. PUBLIC HEALTH RELEVANCE: Understanding retinal signal processing will contribute to the development of therapies for restoring vision in many ways. However, the visual system comprises an extremely complex neural network, and visual system function has still been poorly elucidated. The current proposal will advance the understanding of visual signal processing, and thus contribute to restoring vision for patients.

描述（由申请人提供）：我们的视觉系统将世界感知为时间，空间和颜色的函数。时间（时间）信息，定义了从快速移动到静止的对象的速度，被编码在视觉系统中的时间处理路径中。这些通路根据其神经反应被广泛地分为瞬时通路和持续通路。前者编码快速变化的视觉信息，而后者编码静态信息。早期的工作表明，这些不同的时间处理途径发生在视网膜神经节细胞。两种形态上不同的神经节细胞（α-和<$-神经节细胞）是这两种不同功能通路的起源。最近的研究表明，视网膜双极细胞，这是上游的神经节细胞，是至关重要的视觉信息的并行处理。形态学研究揭示了哺乳动物视网膜双极细胞的10多种亚型，它们可能启动编码不同特征的时间信号的不同通路。到目前为止，还没有研究涉及哺乳动物视网膜双极细胞的每个亚型如何编码时间视觉信息。针对这一研究空白，我的目标是了解ON双极细胞各亚型中时间编码的细胞和分子机制。在这项研究中，我将研究如何在哺乳动物视网膜上的ON双极细胞的每一个亚型编码不同的时间视觉信息。首先，我将研究生理方面的时间编码在每个亚型的ON双极细胞（目的1）。接下来，我将研究时间编码的可能的分子机制：由mGluR 6信号传导（Aim 2）和电压门控通道（Aim 3）引起的细胞内Ca++增加。人们越来越难以忽视对功能性视网膜假体和分子遗传学方法的需求，以恢复患病眼睛的视力。这项研究将提高我们对视网膜网络中并行处理的理解，这将有助于未来设计功能性视网膜假体和视力恢复基因疗法。 公共卫生相关性：了解视网膜信号处理将有助于在许多方面恢复视力的治疗方法的发展。然而，视觉系统包括一个极其复杂的神经网络，视觉系统的功能仍然没有得到很好的阐明。目前的建议将促进对视觉信号处理的理解，从而有助于恢复患者的视力。