In the retina, neural function emerges from the interplay between intrinsic properties of neurons and the pattern, strength and functional characteristics of synaptic communication. Synaptic ion channels and receptors are critical sites for the regulation of cell-to-cell signalling and thus are control points for the modulation of neural function. The overall goal of this research proposal is to understand the molecular mechanisms by which two principle retinal neuromodulatory transmitter systems - DA and NO - modulate gap junctions and ionotropic glutamate receptors. The experimental approach combines electrophysiological, biochemical and molecular techniques to study synaptic modulation in retinal horizontal cells, where these modulatory systems converge. The first objective of the proposal is to elucidate the molecular structure, function and modulation of retinal gap junction channels. The second objective is to gain an understanding of the molecular mechanisms by which the NO/cGMP pathway modulates retinal glutamate receptors. The third objective is to investigate interactions between DA and NO in regulating horizontal cell function.
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