Pharmacology and Physiology of Retinal Ganglion Cells

视网膜神经节细胞的药理学和生理学

基本信息

批准号：
7922365
负责人：
ANDREW T ISHIDA
金额：
$ 8.56万
依托单位：
UNIVERSITY OF CALIFORNIA AT DAVIS
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-30 至 2011-09-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7922365
关键词：
Action Potentials Adult Amblyopia Behavior Brain Cell physiology Cells Code Cyclic AMP Dark Adaptation Dissociation Dopamine Dopamine Agonists Dopamine Receptor Enzymes Exposure to Eye Gated Ion Channel Generations Goals Grant Imaging technology Immunoprecipitation Injection of therapeutic agent Ion Channel Ions Laboratory Research Learning Ligands Light Light Adaptations Methods Molecular Neurotoxins Neurotransmitters Parkinson Disease Pharmacology Phosphorylation Physiology Process Property Publications Rattus Receptor Activation Reporting Retina Retinal Retinal Diseases Retinal Ganglion Cells Role Signal Transduction Strabismus Testing United States National Institutes of Health Vision research Visual Work ganglion cell immunoreactivity novel programs relating to nervous system research study response visual process visual processing voltage

项目摘要

DESCRIPTION (provided by applicant): Vertebrate retinas use "fast" (rapidly acting) neurotransmitters to signal moment-to-moment changes in properties of incident light, and "slow" (modulatory) neurotransmitters to regulate signal flow and processing. The long-term goal of this grant is to understand how slow neurotransmitters modulate action potentials that retinas use to encode their input to the brain. This application proposes to examine how the generation of these spikes changes during the course of a normal day by investigating how dopamine regulates voltage-gated ion channels and inhibits spikes in adult rat retinal ganglion cells. Three hypotheses will be tested: (1) dopamine regulates cAMP levels in mammalian retinal ganglion cells; (2) dopamine inhibits mammalian retinal ganglion cells; and (3) dopamine facilitates light-adaptation in mammalian retinal ganglion cells. Hypothesis #1 will be tested by comparing the cAMP-immunoreactivity of ganglion cells in normal and dopamine-depleted retinas, and in dark-adapted retinas after exposure to dopamine receptor agonists. Hypothesis #2 will be tested by comparing the response of alpha and non-alpha types of ganglion cell to dopamine, by examining effects of D1- and D2-type dopamine agonists and related ligands on spikes and ion current in these cells, and by testing whether dopamine receptor activation results in phosphorylation of voltage-gated Na+ channels. Hypothesis #3 will be tested by comparing the responses of ganglion cells in normal and dopamine-depleted retinas to light and to exogenous current injections. These experiments will be performed by electrophysiological, anatomical, and immunohistochemical methods developed specifically to study ion currents and dopamine responses of retinal ganglion cells. The results of these experiments, especially those comparing normal and dopamine-depleted retinas, may help to understand some of the cellular processes that are compromised in retinas during Parkinson's disease, because low retinal dopamine levels have been found in Parkinson's disease, dopamine depletion by neurotoxins has been reported to produce visual deficits like those found in Parkinson's disease, and dopamine produces fundamentally similar responses in retinal ganglion cells of different species.

描述（由申请人提供）：脊椎动物视网膜使用“快速”（迅速起作用的）神经递质来信号，在入射光的性质中发出力矩到时刻的变化，以及“慢”（调节性）神经递质来调节信号流和处理。这项赠款的长期目标是了解神经递质的慢性调节动作电位如何编码其对大脑的输入。该应用建议通过研究多巴胺如何调节电压门控离子通道并抑制成年大鼠视网膜神经节细胞的尖峰来检查在正常日期内这些峰值的产生如何变化。将检验三个假设：（1）多巴胺调节哺乳动物视网膜神经节细胞的cAMP水平；（2）多巴胺抑制哺乳动物的视网膜神经节细胞；（3）多巴胺促进了哺乳动物视网膜神经节细胞中的光适应。假设＃1将通过比较正常和多巴胺缺失的视网膜中神经节细胞的营地免疫反应性，以及在暴露于多巴胺受体激动剂后的黑暗适应性视网膜中。假设2将通过比较神经节细胞的α和非阿尔法类型对多巴胺的反应，通过检查D1-和D2型多巴胺激动剂的影响以及对这些细胞中的尖峰和离子的相关配体的效果，以及通过测试多巴胺受体受体活化的差异差异差异。假设＃3将通过比较正常和多巴胺缺失的视网膜中的神经节细胞与光和外源性电流注射的反应来测试。这些实验将通过电生理，解剖学和免疫组织化学方法进行，专门研究视网膜神经节细胞的离子电流和多巴胺反应。 The results of these experiments, especially those comparing normal and dopamine-depleted retinas, may help to understand some of the cellular processes that are compromised in retinas during Parkinson's disease, because low retinal dopamine levels have been found in Parkinson's disease, dopamine depletion by neurotoxins has been reported to produce visual deficits like those found in Parkinson's disease, and dopamine produces fundamentally similar不同物种的视网膜神经节细胞中的反应。