SYNAPTIC MECHANISMS IN THE RETINA

本提案的长期目标是了解 神经递质-受体系统编码视觉信息， 视网膜网 前提是专门的突触后受体 能够传递突触前信号的独特成分。 因此，我们认为， 同一神经递质的多种受体的利用 允许信息的多路复用，并且该属性有助于 信息分解的复杂过程发生在 脊椎动物视网膜 该建议的模型系统是视网膜中的GABA系统， 内丛状层 这一层是突触整合的场所 兴奋性和抑制性信号的结合， 神经节细胞发送到大脑。 大多数抑制性输入来自 来自无长突细胞，其中许多是γ-氨基丁酸能的。 过去几年 已经发现了新的GABA受体， 在视网膜中识别。 但这些受体的鉴定还没有 与他们在视网膜功能的理解相匹配， 信息处理. 本提案的目的是澄清 药理学、生理学和这些不同GABA受体的通路。 具体而言，这包括重新检查GABA/A的作用， 受体，以及两种类型的GABA/B受体和 GABA/C受体。 一个工作假设是，GABA/A受体是 专门用于强有力但阶段性的短暂ON和OFF抑制 兴奋和较弱但更紧张的持续ON和OFF抑制 激发GABA/C受体抑制ON通路，并且可能是 参与了视杆细胞和视锥细胞之间的过渡。 而 巴氯芬敏感性GABA/B受体抑制紧张性ON或OFF反应， CACA敏感性GABA/B受体可抑制OFF反应。 电流 钳位和电压钳位实验将被用来测试这个模型 和其他GABA生理学特性。 将使用分子建模 表征激动剂 对每种GABA受体亚型的特异性。 GABA抑制是健康人的一个突出且通常是关键的特征， 神经系统的功能。 因此，调节 GABA能功能长期以来与许多病理学有关， 包括癫痫痉挛和焦虑 一种扩展的理解 GABA受体的多样性及其生理意义将允许 对相关神经系统功能障碍的更精细的治疗。

The long-term objective of this proposal is to understand how multiple neurotransmitter-receptor systems encode visual information within the retinal network. The premise is that specialized postsynaptic receptors are able to convey unique components of a presynaptic signal. Therefore, the utilization of multiple receptors for the same neurotransmitter permits a multiplexing of information and this attribute contributes to the complex process of information decomposition that takes place in the vertebrate retina. The model system for this proposal is the GABA system in the retinal inner plexiform layer. This layer is the site for synaptic integration of excitatory and inhibitory signals that culminates in the message that ganglion cells send to the brain. Most of the inhibitory input comes from amacrine cells, many of which are GABAergic. The last few years have witnessed the discovery of new GABA receptors which were first identified in retina. But the identification of these receptors has not been matched with an understanding of their function in retinal information processing. The aims of this proposal are to clarify the pharmacology, physiology, and pathways of these diverse GABA receptors. Specifically, this includes a re-examination of the role of the GABA/A receptor, and a characterization of two types of GABA/B receptor and the GABA/C receptor. A working hypothesis is that GABA/A receptors are specialized for powerful but phasic inhibition of transient ON and OFF excitation and a weaker but more tonic inhibition of sustained ON and OFF excitation. The GABA/C receptor suppresses the ON pathway and may be involved in the transition between rod and cone vision. While the baclofen sensitive GABA/B receptor suppresses tonic ON or OFF responses, the CACA sensitive GABA/B receptor may suppress OFF responses. Current clamp and voltage clamp experiments will be employed to test this model and other properties of GABA physiology. Molecular modeling will be used to characterize agonist specificity for each GABA receptor subtype. GABA inhibition is a prominent and often critical feature in the healthy functioning of the nervous system. Consequently, drugs that modulate GABAergic function have long been implicated in a number of pathologies, including seizures, spasticity, and anxiety. An expanded understanding of GABA receptor diversity and its physiological implications will permit a more refined treatment of related nervous system dysfunction.