The long-term goal of these experiments remains to understand how peptidergic neurons contribute to information processing in the primate retina, but the experiments proposed for this grant period will focus on a single peptide, cholecystokinin. This peptide has rapid, neurotransmitter-like effects on the activity of ganglion cells in the cat retina, and the goal of these experiments is to predict how cholecystokinin and its antagonists would act in the primate retina. Since the peptide is also a potent miotic, antagonists might be used clinically to prevent post-surgical miosis. If so, it will be important to know how these drugs might affect the retina. During-the previous grant period, cholecystokinin was localized to two kinds of neurons, bipolar cells and amacrine cells. The bipolar cells were shown to be a single morphological type receiving inputs exclusively from blue cones. The amacrine cells appeared to be involved in neural circuits for detecting rapidly-changing stimuli on the basis of their morphology and synaptic connections. The first specific aim is to identify the third-order neurons that receive inputs from the blue cone bipolar cells using light and electron microscopic labeling techniques. The color opponent ganglion cells will be labeled by intracellular injection, and a sub-population of amacrine cells that co-stratify with the ganglion cells will be labeled with immunocytochemical techniques. The working hypothesis is that the blue cone bipolar cells provide input to peptidergic amacrine cells and bistratified ganglion cells. The goal is to describe the neural circuit providing input to blue ON-yellow OFF, color-opponent retinal ganglion cells. The retinas of macaques are vet similar to those of humans, and the results might also suggest why the sensitivity to short wavelengths is lost in many eye diseases. The second specific aim is to identify neurons contacting the cholecystokinin-containing amacrine cells using similar techniques. The working hypothesis is that the cholecystokinin-containing amacrine cells interact with cholinergic amacrine cells, diffuse bipolar cells and parasol ganglion cells. The goal of these experiments is to understand the role of cholecystokinin in shaping the receptive field properties of parasol ganglion cells, also named M cells for their projections to the magnocellular layers of the lateral geniculate nucleus. They are a major type of ganglion cell in primates, and because they may be selectively lost in glaucoma, the results of these experiments may have clinical significance.
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