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.
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