权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Ganglion Cell Function in Retinal Disease

神经节细胞在视网膜疾病中的功能

基本信息

批准号：
8655864
负责人：
Maureen A McCall
金额：
$ 36.8万
依托单位：
UNIVERSITY OF LOUISVILLE
依托单位国家：
美国
项目类别：
财政年份：
2004
资助国家：
美国
起止时间：
2004-02-01 至 2016-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8655864
关键词：
Address Affect Afferent Neurons Age Amacrine Cells Cations Cell physiology Cells Data Defect Detection Development Developmental Delay Disorders Diagnosis Disease Electroretinography Eye Functional disorder Funding Genes Glutamate Receptor Glutamates Goals Human Individual Investigation Lead Light Masks Mediating Modeling Motion Mus Mutant Strains Mice Mutation Nature Nervous system structure Night Blindness Pathway interactions Patients Pattern Peripheral Phenotype Photoreceptors Phylogenetic Analysis Play Primates Principal Investigator Process Property Research Rest Retina Retinal Retinal Diseases Retinal Ganglion Cells Role Sensory Signal Transduction Stimulus Synapses Testing Therapeutic Vision Visual Visuospatial Work disease phenotype ganglion cell information processing luminance mouse model mutant neural circuit programs receptive field receptor research study response scaffold vision development visual process visual processing

项目摘要

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

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细胞处理。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）

项目成果

期刊论文数量（11）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Receptor targets of amacrine cells.

DOI：
10.1017/s0952523812000028
发表时间：
2012-01
期刊：
Visual neuroscience
影响因子：
1.9
作者：
Zhang C;McCall MA
通讯作者：
McCall MA

GABAC receptor-mediated inhibition is altered but not eliminated in the superior colliculus of GABAC rho1 knockout mice.

在 GABAC rho1 敲除小鼠的上丘中，GABAC 受体介导的抑制作用发生改变，但并未消除。

DOI：
10.1152/jn.91001.2008
发表时间：
2009
期刊：
Journal of neurophysiology
影响因子：
2.5
作者：
Schlicker,Katja;McCall,MaureenA;Schmidt,Matthias
通讯作者：
Schmidt,Matthias

Selective glycine receptor α2 subunit control of crossover inhibition between the on and off retinal pathways.

DOI：
10.1523/jneurosci.5341-11.2012
发表时间：
2012-03-07
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
0
作者：
Nobles RD;Zhang C;Müller U;Betz H;McCall MA
通讯作者：
McCall MA

Local signaling from a retinal prosthetic in a rodent retinitis pigmentosa model in vivo.

啮齿动物体内色素性视网膜炎模型中视网膜假体的局部信号传导。