Ganglion Cell Function in Retinal Disease

项目负责人/主要研究者（最后一名、第一名、中间名）： 项目总结/摘要 本研究的目标是了解调控发育的信号机制， 视网膜神经节细胞的视觉功能和空间组织以及它们在视网膜疾病中如何改变。 正常的视觉开始于视网膜，并由光感受器对光的检测启动。平行路径 信息流在光感受器之间的第一突触处启动， 双极细胞，其检测亮度增加和减少和/或在黑暗和光适应下的视觉 条件因此，这些通路在强度上扩展了信息处理的动态范围 域，并增加用于显著环境特征的信息处理的专业化，例如，运动， 方向和大小。这些回路中的信号通过外视网膜和内视网膜中的抑制性输入而被细化， 这些相互作用在视网膜神经节细胞的感受野组织中达到顶点并限定了视网膜神经节细胞的感受野组织。的 感受野是所有物种的所有感觉神经元所共有的基本特性。它定义了类型， 每个细胞编码的环境刺激的范围。因此，了解感受野特性 发展是理解视网膜视觉功能的关键，而神经节细胞是至关重要的部分，因为它们 代表了所有视网膜处理的顶点和视觉处理的其余部分的支架。 由于基本的RF空间组织在神经节细胞中视觉反应的开始时就已经存在， 其发展过程相对难以调查。正常的视力 需要通过去极化和超极化途径的信号传导， 先天性静止性夜盲症（CSNB）患者和小鼠模型中出现的缺陷，其中 消除了去极化双极电池处理。我们有三种独特的CSNB 1小鼠模型， 继续用于探测CSNB背后的突触电路，其中正常的感光功能是 保留。在三个人的GC中自发和视觉诱发反应的变化的性质 突变体为研究感受野组织和神经节细胞的发育提供了一个独特的机会 发信号。感受野组织的系统发育保守性表明，我们在小鼠中的发现 与灵长类动物的周边视网膜处理有关我们认为，这些小鼠的特征 模型代表了一个重要的机会，这是其他小鼠或脊椎动物模型所不能提供的， 这是我们理解CSNB 1疾病机制和正常视网膜发育的关键一步， 和功能 PHS 398/2590（Rev. 11/07）

Program Director/Principal Investigator (Last, First, Middle): PROJECT SUMMARY/ABSTRACT The goals of this research are focused on understanding signaling mechanisms that regulate the development of visual function and spatial organization of retinal ganglion cells and how they are altered in retinal disease. Normal vision begins in the retina and is initiated by photoreceptor detection of light. Parallel pathways of information flow are initiated at the first synapse between photoreceptors and depolarizing and hyperpolarizing bipolar cells, which detect luminance increases and decreases and/or vision under dark- and light-adapted conditions. As a result, the pathways extend the dynamic range of information processing in the intensity domain, and increase specialization of information processing for salient environmental features, e.g., motion, direction and size. Signaling within these circuits is refined by inhibitory inputs in the outer and inner retina and these interactions culminate in and define the receptive field organization of the retinal ganglion cells. The receptive field is a basic property, shared across all sensory neurons in all species. It defines the types and range of environmental stimuli that each cell encodes. Thus, understanding how receptive field properties develop is key to understanding visual function in the retina and the ganglion cells are a vital part because they represent both the culmination of all retinal processing and the scaffold for the rest of visual processing. Because basic RF spatial organization is already present at the onset of visual responses in ganglion cells, the processes underlying their development have been relatively intractable to investigation. That normal vision requires signaling through the depolarizing and hyperpolarizing pathways is amply indicated by the visual defects that occur in patients with and mouse models of congenital stationary night blindness (CSNB), where depolarizing bipolar cell processing is eliminated. We have three unique mouse models of CSNB1 that we will continue to use to probe the synaptic circuitry underlying CSNB, in which normal photoreceptor function is retained. The nature of the changes in spontaneous and visually-evoked responses across GCs in the three mutants provides a unique opening to study the development of receptive field organization and ganglion cell signaling. The phylogenetic conservation of receptive field organization suggests that our findings in the mouse will be relevant to primate peripheral retinal processing. We suggest that the characterization of these mouse models represents a significant opportunity, not afforded by other mouse or vertebrate models and represents a critical step in our understanding both the disease mechanisms in CSNB1 and normal retinal development and function. PHS 398/2590 (Rev. 11/07) Page Continuation Format Page