SYNAPTIC MECHANISMS IN RETINA

抑制性氨基酸在脊椎动物中发挥多种作用 视网膜。 直到最近，人们还认为这些的唯一作用 发射器是对氯门控通道的直接作用。 现在是 显然，GABA 和甘氨酸调节其他通道，通过 第二信使，并调节其他受体，例如 NMDA 型 谷氨酸受体。 基于这些新发现，该提案提供了 重新检查抑制性氨基酸的作用，重点关注 GABA能系统。 目标之一是更多地了解 GABAb 受体系统。 一个具体目标是确定是否有亚型 GABAb 受体存在于视网膜中，描述其电导 机制及其对电压和光相关特性的影响 视网膜神经元。 GABAb 受体对特异性的影响 信息通路，特别是对抗性周围反应 远端视网膜和近端视网膜的方向敏感性， 将被调查。 另一个目标是绘制本地化的效果图 GABA 和甘氨酸沿着无长突树突的应用 神经节细胞。 一个具体目的是检验 GABAa 和 当甘氨酸靠近体细胞施加时会产生超极化，但 当应用于树突的远端部分时，会发生去极化，并且 测试GABAb受体是否集中在远端 树突。 GABA 和 GABA 之间似乎也存在相互作用。 视网膜中的甘氨酸受体，这可能代表了交叉 配体作用，一种对 GABA 和 GABA 均敏感的受体亚型 甘氨酸，或异源脱敏。 机制及 将研究这种相互作用的重要性。 此外， 假定的 GABAc 受体在视网膜中可能具有重要意义 被探索。 总的来说，这项研究将试图提供一个 了解 GABA 受体亚型在视网膜中的作用 突触机制和信息处理。

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.