MECHANISMS OF RETINAL ELECTRICAL SYNAPTIC PLASTICITY

视网膜电突触可塑性机制

• 批准号: 2259861
• 负责人: DOUGLAS G MCMAHON
• 金额: $ 6.48万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-04-01 至 1999-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2259861
• 关键词: acidity /alkalinity; biophysics; calcium flux; cell adhesion; cyclic GMP; dopamine; electrophysiology; gap junctions; membrane biogenesis; neural plasticity; neural transmission; nifedipine; nitric oxide; receptor coupling; retina; synapses; voltage /patch clamp; zebrafish

Modulation of synaptic communication between neurons is a fundamental mechanism by which the nervous system responds to changing levels of stimuli, reflects previous experience and shapes functional connections during development. The broad goal of the research proposed here is to gain an understanding of the mechanisms of electrical synaptic plasticity at a molecular level using synaptic modulation in the outer plexiform layer of the retina as an experimental system. The proposed experiments focus on three specific aims; (1) extending successful studies of synaptic modulation at the single channel level to include modulation by nitric oxide, cGMP and pH, in addition to dopamine, (2) accelerating efforts in progress directed at cloning cDNAs for teleost retinal gap junction channel genes, and (3) expanding the scope of research to examine the regulation of assembly and maintenance of electrical synapses by dopamine, cell calcium and cell-cell adhesion. Successful completion of these experiments will contribute in a fundamental way to our understanding of the modulation of electrical synaptic transmission in the nervous system. This basic knowledge should be useful in understanding the pathophysiology of epilepsy, Parkinsonism, schizophrenia and senescence, where these processes are apparently deranged.

神经元之间突触通信的调节是基本的 神经系统对变化水平的反应机制 刺激，反映以前的经验并塑造功能连接 在开发过程中。 这里提出的研究的广泛目标是 了解电突触可塑性的机制 在分子水平上使用突触调制 视网膜层作为实验系统。 提出的实验 专注于三个特定目标； （1）扩展成功的研究 在单个通道级别的突触调制，包括 一氧化氮，CGMP和pH，除了多巴胺，（2）加速 正在进行的努力针对克隆cDNA用于标题视网膜间隙 连接通道基因，以及（3）将研究范围扩展到 检查组装的调节和电气突触的维护 通过多巴胺，细胞钙和细胞 - 细胞粘附。 成功完成 这些实验将以基本的方式贡献 了解电气突触传播的调制 神经系统。 这种基本知识应该在 了解癫痫，帕金森主义的病理生理学， 精神分裂症和衰老，这些过程显然是 混乱。