The long term objective is to understand the structure and function of human and macaque monkey retinal ganglion cells and the neural basis for parallel chromatic and achromatic signal pathways through the inner retina. Major gaps exist in our understanding of the functional organization of the primate retina. Little is known of the relationship between the anatomy and physiology of the major cell types or about the retinal circuitry that links cone photoreceptors to ganglion cell types. More crucially, detailed knowledge of human retinal cell types is also extremely limited, lagging far behind a rapidly growing understanding of macaque retinal neurons. In each case major technical problems in working with the primate and human retina have been difficult to overcome. Experiments outlined in this proposal address each of these problems, applying new techniques developed in the previous project period to both macaque and human retina. The following specific aims are proposed: 1) To complete the first detailed analysis of the dendritic morphologies and spatial densities of human retinal ganglion cell types by using intracellular injection techniques in a new in vitro preparation of the intact human retina. 2) To directly determine the light responses of morphologically identified ganglion cell types in a new in vitro preparation of the macaque retina, specifically testing the hypothesis that the major ganglion cell types of the retinogeniculate pathway, the midget, small bistratified and parasol ganglion cells correspond respectively to the red-green, blue-ON and phasic, non-opponent cell types. 3) To determine the links between three identified cone bipolar cell types the (flat midget bipolar, the B3 diffuse bipolar and the blue cone bipolar) and the three major ganglion cell types, by combining selective immunostaining of bipolar cells with intracellular staining of ganglion cells. 4) To determine the chromatic identity of cone bipolar synaptic input to midget ganglion cell dendritic trees y combining electron microscopic, serial section reconstruction of bipolar contacts onto the dendrites of physiologically identified midget ganglion cells. Correlating the anatomy, physiology and cone bipolar connections for the major primate ganglion cell types will contribute to our understanding of the neural basis for the chromatic and achromatic visual pathways. The first detailed characterization of the human ganglion cell types will also contribute to understanding the neural basis of human visual performance and the cellular basis of retinal diseases, such as glaucoma, that effect cells of the inner retina.
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