This application proposes to continue our ongoing studies of the mechanisms of spontaneous rhythmic activity and the establishment of functional synaptic circuits in the developing mammalian retina. It will test two hypotheses: (1) the spontaneous waves that appear during two different developmental stages (conventional and ribbon synaptogenesis in the inner retina) are produced by different networks of intrinsic oscillators; (2) the complex, asymmetric synaptic circuitry involving starburst cells is established by a process of coordinated reorganization and refinement of synaptic connectivity and synaptic function. To test these hypotheses, we propose to integrate several cutting-edge electrophysiological techniques, which will enable the direct measurement of synaptic function and synaptic connectivity in an anatomically well-defined and functionally well-specified network at various developmental stages. The proposed studies will pursue three specific aims: (1) to determine the cellular mechanisms underlying spontaneous retinal waves, (2) to determine the mechanism and function of synaptic interaction during synaptogenesis.and retinal waves, (3) to understand the development of starburst synaptic function and circuitry. Results from these studies will allow the integration of functional and anatomical information about the developing retina in a way previously unattainable in other experimental settings and may lead to better understanding of visual system development in health and diseases. ? ? ?
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