This grant proposes to continue the study of the physiological and pharmacological properties of synapses mediating the center-surround receptive field organization of retinal bipolar cells. Living retinal slices will be used in this study because they provide the advantages of both the whole retina and the isolated cell preparations: retinal slices are intact enough so that most synapses are functional and excitable by presynaptic current injection or by light (in fact, excellent light responses can be recorded from all cell types in the retinal slices); and cells in slices are accessible enough so that multi-electrode recordings can be performed under visual control. Pharmacological agents can be applied either grossly to the whole slice via the bath with virtually no diffusion barrier, or locally to individual cells via pressure ejection or iontopheresis micropipettes. Synaptic transmission from rods, cones, horizontal cells and amacrine cells to bipolar cells will be individually studied when these synapses are activated by light, presynaptic polarization, or by application of neurotransmitters. Input-output relations, postsynaptic conductance changes, kinetics and ionic components of postsynaptic currents, and voltage gains of each synapse will be determined. Moreover, postsynaptic events elicited by neurotransmitters and the characteristics of postsynaptic receptors in bipolar cells will be examined. Specifically, experiments in this proposal are designed to address the questions of (1) whether rods and cones exert the same physiological and pharmacological actions on bipolar cells; (2) whether depolarizing and hyperpolarizing bipolar cells have similar or different physiological and pharmacological responses to the same synaptic inputs; (3) what postsynaptic actions horizontal cells and amacrine cells exert on bipolar cells and what roles these synapses play in mediating the bipolar cell surround responses; and (4) whether there is a clear relationship between neurotransmitter-specific and function-specific pathways in the retina. In the short term, results obtained will increase our understanding of the basic synaptic mechanisms which mediate the function of retinal bipolar cells, and will provide crucial tests for the identification of retinal neurotransmitters. In the long term, the objective is to integrate the results obtained into a detailed description of how individual membrane and synaptic events are responsible for organizing the center-surround receptive fields of retinal bipolar cells - the first stages of information processing in the visual system.
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