The long term goal of this proposed work is to elucidate the biochemical, anatomical and electrophysiological basis of vision. Emphasis will be on the functioning of the neural retina with a primary goal of understanding how the photoresponses generated by the rods and cones are synaptically transmitted by way of two or more intermediary classes of neuron to the ganglion cells. The secondary long-term goal is to develop an understanding of the pathophysiology of retinal disease processes and inborn errors of metabolism. The approach is an experimental one that focuses at the cellular level. Microelectrode techniques will probe the electrical behavior of individual neurons and the biochemical processes of synaptic transmission.
The specific aims of this project period are to identify the transmitter substance released by photoreceptors and to determine by what biochemical and pharmacological means this release is controlled and regulated. For this purpose we intend to develop methods to detect directly the transmitter substance as it is secreted from the rods and cones.
A second aim of this project period is to determine the action that the photorecptor neurotransmitter has on the second order neurons in the retina. Among the actions to be identified are the types of postsynaptic receptor proteins activated by the neurotransmitter, and the ionic specificity, voltage dependencies, and kinetics of the conductance channels activated by the neurotransmitter.
A third aim i s to elucidate the synaptic mechanisms that excite and inhibit the ganglion cells. The ganglion cells, being the output neurons of the retina, integrate the information coming from the more distal parts of the retina. The pharamcology and biophysical parameters of the synaptic inputs to the ganglion cells will be investigated.
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