This competing renewal proposal is to study electrophysiological and pharmacological properties of the spontaneous rhythmic excitation in the developing mammalian retina. Using patch-clamp recording directly from starburst amacrine cells and ganglion cells in the retina, we can now, for the first time, conduct cellular and electrophysiological studies of the spontaneous retinal wave at a level presynaptic to retinal ganglion cells. We can also begin to investigate the interaction between ganglion cells and retinal interneurons during development. The experiments proposed here will be performed in a novel preparation, in which patch- clamp recording are made simultaneously from pairs of identified starburst and ganglion cells in the whole-mount neonatal retina (Zhous, Journal of Neuroscience, 1998). This experimental approach allows for detailed electrophysiological and pharmacological and pharmacological characterization of coordinated characterization of coordinated retinal activities at a cellular and synaptic level previously unattainable. We will focus on three specific aims (1) to determine the intrinsic membrane properties of starburst amacrine cells and ganglion cells during postnatal development, (2) to determine the physiological and pharmacological characteristics of spontaneous rhythmic activities in starburst amacrine cells and ganglion cells in the developing retina, and (3) to understand the interaction among starburst cells and ganglion cells during rhythmic bursts of spontaneous excitation in the developing retina. Results from this study will help us understand what and how neurotransmitter systems affect cholinergic amacrine cells in the developing retina and how the cholinergic system, in turn, influences spontaneous retinal waves. These results will also provide much needed experimental data for the model of neuronal interactions in the developing retina, thus allowing better understanding of visual development and retinal processing in health and diseases.
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