Inhibitory amino acids play a multiplicity of roles in the vertebrate retina. Until recently it was thought that the sole effect of these transmitters was a direct action on chloride gated channels. It is now evident that GABA and glycine regulate other channels, act through second messengers, and modulate other receptors such as the NMDA-type glutamate receptor. Based on these new findings, this proposal offers to re-examine the actions of inhibitory amino acids, concentrating on the GABAergic system. One goal is to learn more about the GABAb receptor system.
A specific aim i s to determine if subtypes of the GABAb receptor are present in the retina, describe their conductance mechanisms, and their effects on voltage and light dependent properties of retinal neurons. The effect of GABAb receptors on specific information pathways, particularly the antagonistic surround response in the distal retina and orientation sensitivity in the proximal retina, will be investigated. Another goal is to map the effect of localized applications of GABA and glycine along the dendrites of amacrine and ganglion cells.
A specific aim i s to test the hypotheses that GABAa and glycine produce hyperpolarizations when applied near the soma but depolarizations when applied to distal portions of dendrites, and to test whether GABAb receptors are concentrated at the distal ends of dendrites. There also appears to be an interaction between GABA and glycine receptors in the retina, which may represent a crossover in ligand action, a receptor subtype that is sensitive to both GABA and glycine, or heterologous desensitization. The mechanism and significance of this interaction will be studied. In addition, the possible significance in the retina of the putative GABAc receptor will be explored. Overall, this research will attempt to provide an understanding of the roles GABA receptor subtypes play in retinal synaptic mechanisms and information processing.
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