This proposal describes investigations into the addition of new neurons and the resultant reorganizations of synaptic connectivity which occur in the visual system during postembryonic growth of goldfish. Previous work has shown that rods are produced from special precursor cells and continuously inserted into the differentiated retina even in adults. The proposed studies seek to discover how the new rods are integrated into the preestablished retinal circuitry, what are the functional consequences of the delayed and prolonged development of rods, and what are the rules that govern neurogenesis in the normal and regenerating retina. There are five Specific Aims. 1. To describe synaptogenesis of photoreceptor cells (rods) in the larvae and juvenile retina of goldfish. 2. To examine the development of the retinomotor response and to determine the neural circuitry involved. 3. To examine the relationship between Muller glia and migrating neuronal precursors. 4. To determine whether mechanical stretch modulates the rate of cell proliferation in the retina and whether cell death is involved. 5. To examine the specificity of the rod precursors population using immunocytochemistry and to challenge the rod precursors to lose their specificity when the retina regenerates following destruction by metabolic toxins. These experiments are relevant to two central issues in developmental neurobiology. The first is: how do neurons adjust to changes in the relative numbers or proportions of other neurons with which they form connections? The second is: how do cellular interactions between neurons and glial cells influence the development of structure in the brain? The studies on retinal regeneration will also provide important information about repair and replacement of neurons in the central nervous system.
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