STRUCTURAL NEUROCHEMISTRY OF RETINAL CIRCUITS

视网膜回路的结构神经化学

• 批准号: 2634374
• 负责人: ROBERT E MARC
• 金额: $ 23.82万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-03-01 至 2000-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2634374
• 关键词: acetylcholine; alternatives to animals in research; amacrine cells; aminoacid; chemical binding; dicarboxylate; electron microscopy; electrophysiology; gamma aminobutyrate; goldfish; homeostasis; hypoxia; image processing; immunocytochemistry; neuroanatomy; neurochemistry; neurophysiology; neurotransmitter transport; neurotransmitters; retina; retinal bipolar neuron; retinal ganglion; synapses

The long range objectives of this work are to elucidate homeostatic signatures for all cells of the normal retina, explore the dynamics of these signatures under both physiological and pathophysiological challenge and use such signatures to map excitatory networks of the vertebrate retina. We believe this program to be of significance for (1) understanding the details of organization which all artificial vision systems must likely mimic and (2) managing the retinal microenvironment when homeostatic control of pivotal molecular constituents is compromised by trauma, environmental insults, or genetic/acquired disease. Model systems: goldfish, rabbit. Specific Aim 1 is a comprehensive characterization of the amino acid/metabolite signatures for all cells of the vertebrate retina by pattern recognition of the natural amino acids, special amino acids and key carboxylic acids. It will be achieved through immunochemical mapping of serial ultrathin (40 nm) optical microscopic images, image registration and N-dimensional pattern recognition. Specific Aim 2 is a program to define signature responses of all vertebrate retinal cells to photic adaptation, neurochemical drive, hypoxia/hypoglycemia, osmotic challenge. Regulation by dopamine or NO, neurochemical activation through APMA/kainate- or NMDA-gated paths, impacts of hypoxia and hypoglycemia and osmotic challenges will be investigated in vitro and analyzed by both pattern recognition techniques and laminar profiling of the inner plexiform layer. Specific Aim 3 extends the analysis of retinal circuitry by mapping the retinal flow of excitatory signals gated by extracellular glutamate/ACh and intracellular cGMP through non-selective cation channels. Excitation events will be detected with IgGs against channel-permeating cations and mapped into retinal populations with single-cell resolution. Specific Aim 4 is the completion of a comprehensive catalogue of cyprinid retinal neurons using signature techniques superimposed upon both Golgi impregnation and ultrastructural imagery. This catalogue will assign not only a primary neurotransmitter but also a comprehensive signature to a specific morphology and synaptology.

这项工作的远距离目标是阐明体内平衡 正常视网膜所有细胞的签名，探索动力学 这些特征在生理和病理生理学下 挑战并使用此类签名来映射 脊椎动物视网膜。我们认为该计划对（1）具有重要意义 了解所有人造视觉的组织细节 系统可能必须模仿，并且（2）管理视网膜微环境 当关键分子成分的稳态控制被损害 通过创伤，环境侮辱或遗传/获得性疾病。模型 系统：金鱼，兔子。 特定目标1是氨基的全面表征 通过脊椎动物视网膜所有细胞的酸/代谢物特征 天然氨基酸，特殊氨基酸和 关键的羧酸。它将通过免疫化学映射实现 串行超薄（40 nm）光学显微镜图像的图像 注册和n维模式识别。 特定目标2是一个计划定义所有人的签名响应的程序 脊椎动物视网膜细胞对光学适应，神经化学驱动， 低氧/低血糖，渗透挑战。多巴胺或否。 通过APMA/Kainate或NMDA门控路径的神经化学激活， 缺氧，低血糖和渗透挑战的影响将是 在体外研究并通过两种模式识别技术进行了分析 和内丛状层的层状分析。 特定目标3通过映射视网膜电路分析 细胞外谷氨酸/ACH门控的兴奋信号的视网膜流动 通过非选择性阳离子通道和细胞内CGMP。励磁 将使用IgG检测到事件，以针对通道渗透阳离子和 用单细胞分辨率映射到视网膜种群中。 特定目标4是完成塞普林蛋白的综合目录 使用签名技术叠加在两个高尔基体上的视网膜神经元 浸渍和超微结构图像。此目录不会分配 只有主要神经递质，也是一个全面的签名 特定的形态和突触学。