RETINAL HORIZONTAL CELLS--PHYSIOLOGY AND PHARMACOLOGY

水平细胞是非尖峰的局部环路中间神经元， 脊椎动物外丛状层的横向相互作用 视网膜。尽管对水平细胞生理学进行了大量研究 还没有系统地研究经济增长的所有投入产出关系。 单个物种中的水平细胞。拟议研究的目标是 来描述负责产生 非洲爪哇视网膜的水平细胞反应。特别强调的是 放置在杆和锥体信号之间的相互作用上 水平单元格，非洲爪哇水平单元格是一个问题 特别适合，因为它们从杆和杆接收混合输入 圆锥体。这些结果可能与理解杆-锥体相互作用有关 人类的视网膜。通过设计一种合适的“鸡尾酒” 从药物上将细胞从它的一些输入中分离出来 可以监测与突触相关的电导变化 传递和药物应用，并确定突触和 影响水平细胞反应的固有膜通道 灯。以下方法将用于剖析各种不同的 影响细胞反应的因素：1)杆状和锥状输入将 通过适当选择适应条件而被隔离。2)突触 锥体的反馈和来自丛状细胞的突触输入将是 通过视网膜与GABA激动剂和拮抗剂的超融合来操纵的 和甘氨酸。3)水平单元间的电耦合 会因使用解偶联剂而减弱。4)电压 和水平细胞膜固有的随时间变化的电导 会被特定的离子通道阻断所阻断 探员们。获得的数据将提供对几个基本和AS的洞察 视网膜神经生理学中尚未解决的问题包括：1)什么是 杆状和锥体介导的水平细胞区别的基础 反应？2)视网膜的适应状态如何影响 水平细胞反应？3)突触如何反馈到锥体， 神经丛间细胞的突触输入和相互间的电耦合 水平单元格有助于单元格的响应？4) 神经递质对水平细胞的反应有贡献 它们的作用机制？5)电压依赖的电导是如何 会影响完整视网膜的水平细胞反应吗？

Horizontal cells are non-spiking local circuit interneurons that mediate lateral interactions in the outer plexiform layer of the vertebrate retina. Despite numerous investigations of horizontal cell physiology there has been no systematic study of all the input-output relations of the horizontal cell in a single species. The goal of the proposed research is to characterize the mechanisms responsible for the generation of the horizontal cell response in Xenopus retina. Special emphasis will be placed on the interactions between rod and cone signals on the same horizontal cell, a problem for which Xenopus horizontal cells are particularly well suited because they receive mixed input from rods and cones. Results may be relevant to understanding rod-cone interactions in the human retina. By designing a suitable 'cocktail' that pharmacologically isolates the cell from some of its inputs it will be possible to monitor conductance changes associated with synaptic transmission and drug application and to identify the role of synaptic and intrinsic membrane channels in shaping the horizontal cell's response to light. The following methods will be used to dissect out the various factors contributing to the cell's response: 1) Rod and cone inputs will be isolated by appropriate choice of adaptational conditions. 2) Synaptic feedback onto cones and synaptic input from interplexiform cells will be manipulated by superfusing the retina with agonists and antagonists of GABA and glycine, respectively. 3) Electrical coupling between horizontal cells will be attenuated by the application of an uncoupling agent. 4) Voltage and time-dependent conductances intrinsic to the horizontal cell membrane will be blocked by the application of specific ion-channel blocking agents. The data obtained will provide insight into several basic and as yet unresolved problems in retinal neurophysiology including: 1) What is the basis for the differences between rod and cone mediated horizontal cell responses? 2) How does the adaptational state of the retina influence the horizontal cell response? 3) How does synaptic feedback onto cones, synaptic input from interplexiform cells and electrical coupling between horizontal cells contribute to the cell's response? 4) Which neurotransmitters contribute to the horizontal cell's response and what is their mechanism of action? 5) How do voltage-dependent conductances influence the horizontal cell response in the intact retina?