This proposal will study how the circuitry of the vertebrate retina translates the visual scene into a complex language of electrical impulses in the optic nerve. One of the largest gaps in neuroscience is in the explaining of systems-level processes like vision in terms of cellular-level mechanisms. The retina is one of the best places in which to bridge this gap because of the basic properties that are already known of its cell types, and because of growing knowledge about the complex, adaptive visual processing the retina performs. The specific goals of this project are to 1) Directly measure functional connections of amacrine cells, a diverse type of inhibitory interneuron, to the output of the retina, and determine the overall organization of these circuits. 2) Understand how amacrine cells change the visual responses of retinal ganglion cells. 3) Understand how these functional properties change during adaptation to the visual scene. A number of techniques are combined to create a general program for determining how the retinal circuit functions. An array of extracellular electrodes is used to record the light responses of many ganglion cells at once. Simultaneously, intracellular recordings monitor the visual responses of interneurons in the circuit. Injection of current into these interneurons allows direct measurement of functional connections, revealing how the interneuron's output affects the overall output of the operating circuit. The resulting large sets of data are summarized with mathematical models that confirm our understanding of the neural circuitry. This combined approach promises general insight into the function of neural circuits. The loss of retinal function is a prevalent aspect of many widespread diseases that produce blindness, including retinitis pigmentosa and macular degeneration. It is expected that learning how the retinal circuitry processes visual scenes will aid in the development of a retinal electronic prosthetic device and early diagnostic tests for the progression of retinal disorders. ? ? ?
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