NEURAL SIGNALLING IN THE RETINA

我们建议研究视觉转导的分子机制， 视网膜杆和信号流到视网膜神经节细胞。 膜片钳方法将他用来问以下问题， cGMP激活的阳离子通道，产生视杆细胞对光的反应：1） CGMP如何激活通道调节离子流 通过它？配体控制的门相对于 阳离子结合位点？2)通道的共价修饰是否调节了 通道对cGMP的反应？什么样的信号控制着修改， 分子机制？3)什么是径向分布 在视杆细胞外段有cGMP激活的通道吗4)通过什么机制 二价阳离子如Ni++和Zn++增强通道对 cGMP？二价阳离子的增强作用调节通道敏感性吗 在生理条件下？5)在单通道级别， 通道的开放态电导和门控动力学取决于cGMP 浓度和膜电位？ 使用一种新的多电极记录方法，我们将研究相关性， 视网膜神经节自发和光诱发棘波放电 细胞，问：1）在黑暗和昏暗的光，如何做的相关性， 在附近的视网膜神经节细胞的冲动之间依赖于细胞类型，细胞 分离与时间？2)神经节细胞的空间分布是怎样的 不同的功能类型？3)神经节细胞的反应 一个单一的视紫红质分子的光异构化？ 回答这些问题可能有助于更清楚地了解 疾病中的视觉障碍。

We propose to investigate the molecular mechanism of visual transduction in retinal rods and the flow of signals to retinal ganglion cells. Patch clamp methods will he used to ask the following questions about the cGMP-activated cation channel that generates the rod response to light: 1) How does activation of the channel by CGMP regulate the flow of ions through it? Where is the ligand-controlled gate located relative to the cation binding site? 2) Does covalent modification of channels regulate the channel response to cGMP? What signals control modification, and what is the molecular mechanism? 3) What is the radial distribution of cGMP-activated channels on the rod outer segment? 4) By what mechanism do divalent cations such as Ni++ and Zn++ potentiate the channel's response to cGMP? Does potentiation by divalent cations regulate channel sensitivity under physiological conditions? 5) At the single channel level, how do the open state conductances and gating kinetics of the channel depend on cGMP concentration and membrane potential? Using a new multielectrode recording method we will study correlations in the spontaneous and light-evoked spike discharges of retinal ganglion cells, asking: 1) In darkness and dim light, how do the correlations between impulses in nearby retinal ganglion cells depend on cell type, cell separation and time? 2) What is the spatial distribution of ganglion cells of different functional types? 3) What is the response of the ganglion cell population to photoisomerization of a single rhodopsin molecule? Answers to these questions may help to provide a clearer understanding of visual disturbances in disease.