METABOTROPIC GLUTAMATE RECEPTORS ON AMACRINE CELLS

无精细胞上的代谢型谷氨酸受体

基本信息

批准号：
6518597
负责人：
EVANNA L GLEASON
金额：
$ 9.92万
依托单位：
LOUISIANA STATE UNIV A&M COL BATON ROUGE
依托单位国家：
美国
项目类别：
财政年份：
1998
资助国家：
美国
起止时间：
1998-07-01 至 2003-06-30
项目状态：
已结题

项目摘要

In the retina, visual information is processed by the synapses between neurons. The wealth of neuromodulators and neuromodulator receptors that have been discovered in the retina so far suggest that this synaptic circuitry is not fixed but instead is adaptable to changing conditions in the visual world. One type of modulation that is fairly well understood is light-dark adaptation but the preponderance of modulatory substances in the retina suggests that other types of adaptation also occur. This proposal addresses the physiological role of one type of neuromodulator receptor, the metabotropic glutamate receptor (mGluR). This receptor is a G protein-coupled receptor that is activated by glutamate and linked to cytosolic second messenger cascades. In other systems, activation of these receptors has been shown to engender dramatic changes in the behavior of neurons and their synapses, but the function of these receptors in the retina is largely unexplored. The proposed experiments utilize a unique preparation of cultured retinal neurons cells derived from the embryonic chick retina that provides both isolated cells and synaptic pairs of cells that are amenable to study with electrophysiological techniques. We propose to investigate the role of mGluR activation in retinal amacrine cells. In the first aim, experiments are designed to explore the expression of mGluRs by retinal amacrine cells using immunocytochemical methods. This will tell us which mGluRs have the potential to modulate and will help define functional classes of amacrine cells in the retina and in culture. In aim 2, isolated amacrine cells will be examined using voltage clamp recording techniques to determine the ability of mGluR activation to modulate the ion channels important in synaptic transmission. Modulation of any of these channels will lead to hypotheses on the effects of mGluR activation on synaptic transmission. The experiments in Aim 3 are designed to test these hypotheses by recording from synaptically connected pairs of amacrine cells. These studies will lead the way to understanding the role glutamate plays in reorganizing synaptic circuits in the retina.

在视网膜中，视觉信息是通过之间的突触处理的神经元。神经调节剂和神经调节剂受体的财富到目前为止在视网膜中发现的突触电路不是固定的，而是适合更改的视觉世界中的条件。公平的一种调制众所周知的是浅黑色改编视网膜中的调节物质表明其他类型的也会发生适应。该建议涉及生理角色一种类型的神经调节剂受体，代谢性谷氨酸受体（mglur）。该受体是G蛋白偶联受体，被谷氨酸激活，并链接到胞质第二信使级联。在其他系统中，这些受体的激活一直是显示出神经元及其行为的巨大变化突触，但是这些受体在视网膜中的功能很大未探索。提出的实验利用了独特的准备源自胚胎鸡视网膜的培养的视网膜神经元细胞提供了孤立的细胞和突触对的细胞对可以使用电生理技术研究。我们建议研究MGLUR活化在视网膜无大细胞中的作用。在第一个目的，实验旨在探索表达使用免疫细胞化学方法通过视网膜团体细胞mglurs。这将告诉我们哪些mglurs有可能调节并将有所帮助定义视网膜和在文化。在AIM 2中，将使用电压夹具记录技术以确定mglur的能力激活以调节突触中重要的离子通道传播。这些渠道中的任何一个都会导致假设mglur激活对突触传播的影响。 AIM 3中的实验旨在通过从突触连接的无结向细胞对记录。这些研究将导致理解谷氨酸在在视网膜中重组突触电路。