SYNAPTIC MECHANISMS IN THE VERTEBRATE RETINA

脊椎动物视网膜的突触机制

• 批准号: 3261120
• 负责人: MALCOLM M SLAUGHTER
• 金额: $ 14.28万
• 依托单位: STATE UNIVERSITY OF NEW YORK AT BUFFALO
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-08-01 至 1995-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3261120
• 关键词: Amphibia; GABA receptor; Urodela; amacrine cells; aminoacid inhibitor; dendrites; gamma aminobutyrate; glycine; glycine receptors; membrane potentials; neural conduction; neural information processing; neural inhibition; neural transmission; neuropharmacology; neurotransmitters; photostimulus; receptor binding; retina; retinal ganglion; space perception; stimulant /agonist; synapses; voltage /patch clamp

Inhibitory amino acids play a multiplicity of roles in the vertebrate retina. Until recently it was thought that the sole effect of these transmitters was a direct action on chloride gated channels. It is now evident that GABA and glycine regulate other channels, act through second messengers, and modulate other receptors such as the NMDA-type glutamate receptor. Based on these new findings, this proposal offers to re-examine the actions of inhibitory amino acids, concentrating on the GABAergic system. One goal is to learn more about the GABAb receptor system. A specific aim is to determine if subtypes of the GABAb receptor are present in the retina, describe their conductance mechanisms, and their effects on voltage and light dependent properties of retinal neurons. The effect of GABAb receptors on specific information pathways, particularly the antagonistic surround response in the distal retina and orientation sensitivity in the proximal retina, will be investigated. Another goal is to map the effect of localized applications of GABA and glycine along the dendrites of amacrine and ganglion cells. A specific aim is to test the hypotheses that GABAa and glycine produce hyperpolarizations when applied near the soma but depolarizations when applied to distal portions of dendrites, and to test whether GABAb receptors are concentrated at the distal ends of dendrites. There also appears to be an interaction between GABA and glycine receptors in the retina, which may represent a crossover in ligand action, a receptor subtype that is sensitive to both GABA and glycine, or heterologous desensitization. The mechanism and significance of this interaction will be studied. In addition, the possible significance in the retina of the putative GABAc receptor will be explored. Overall, this research will attempt to provide an understanding of the roles GABA receptor subtypes play in retinal synaptic mechanisms and information processing.

抑制性氨基酸在脊椎动物中起着多种作用 视网膜。 直到最近，人们还认为， 递质是对氯门控通道的直接作用。 现在 很明显，GABA和甘氨酸调节其他通道，通过 第二信使，并调节其他受体，如NMDA型 谷氨酸受体。 根据这些新发现，该提案提供了 重新检查抑制性氨基酸的作用，集中在 GABA能系统 一个目标是更多地了解GABAb 受体系统 一个具体的目标是确定是否亚型的 GABAb受体存在于视网膜中，描述其电导 机制，以及它们对电压和光依赖性的影响 视网膜神经元。 GABAb受体对特异性 信息通路，特别是拮抗性周围反应， 远侧视网膜和近侧视网膜中的方向灵敏度， 将进行调查。 另一个目标是绘制本地化的 GABA和甘氨酸沿着无长突树突的应用， 神经节细胞 一个具体的目的是测试假设，GABA a和 甘氨酸在靠近索马时产生超极化， 当施加到树突的远端部分时， 测试GABAb受体是否集中在远端， 树突 GABA和GABAA之间似乎也存在相互作用， 视网膜中的甘氨酸受体，这可能代表了一个交叉， 配体作用，一种受体亚型，对GABA和 甘氨酸或异源脱敏。 的机理和 将研究这种相互作用的意义。 此外该 假定的GABAc受体在视网膜中的可能意义将 被探索。 总的来说，这项研究将试图提供一个 GABA受体亚型在视网膜神经元凋亡中的作用 突触机制和信息处理。