The long-term objective is to understand the structure and function of the primate parallel visual pathways that originate at the first synapse in the retina, where signals from photoreceptors are transmitted to bipolar and horizontal cells. The major goals are to determine the structure of the trichromatic cone mosaic, the physiology of the cone photoreceptors, and how signals are transmitted from each cone type to a diverse array of morphologically distinct bipolar and horizontal cell types. New methods of photopigment imaging, intracellular physiology and electron microscopy will be applied to an in vitro preparation of the macaque monkey retina. The four specific aims are: (1) to determine the spatial distribution and synaptic connections of the long (L) and middle (M) wavelength-sensitive cone types using a new method of reflection densitometry and electron microscopy: the hypothesis that the L and M cone types form non-randomly distributed submosaics and are linked to synaptically distinct bipolar cells pathways to the inner retina will be tested; (2) to determine the spatial structure of the cone receptive field, testing the hypothesis that cones have a center-surround receptive field organization and that the surround confers color opponency to the light response; (3) to determine the cone connections and receptive field structure of morphologically identified cone bipolar cell types: the hypothesis that distinct cone bipolar cell types transmit both luminance and chromatically opponent signals in parallel to the inner retina will be tested; and (4) to determine the functional connections among horizontal, bipolar and cone cell types. The hypothesis that horizontal cells make feedback connections to cones and feedforward connections to bipolar cells, thereby generating the inhibitory receptive field surround in both cones and bipolar cells, will be tested. The resulting data will permit an exploration of the functional microcircuitry of the outer retina and its role in color vision, temporal sensitivity and light adaptation. Because the outer retina of the macaque is so similar to that of the human, it will provide the best and most detailed structure-function model of the human outer retina. The results are expected to contribute to a new foundation for understanding the cellular origins of human retinal disease.
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