The mechanisms and function of spontaneous neural activity in the developing mammalian retina will be studied. Immature retinal neurons spontaneously generate correlated activity in the form of waves of action potentials that sweep across the retinal ganglion cell layer. These """"""""retinal waves"""""""" occur during the developmental period when retinal ganglion cell axons are segregating into eye-specific layers in the lateral geniculate nucleus. Experiments using a combination optical imaging, single cell electrophysiology, and multielectrode array recordings are proposed to investigate the mechanisms of inter-cellular coupling that underlie the generation of retinal waves. First, using knockout mice, we will identify the role of a particular gap junction coupled network in generating the correlation structure of spontaneous action potentials in retinal ganglion cells. Second, we will study the mechanisms underlying the ability of the neuromodulators adenosine and GABA to powerfully modulate network activity. One result of this work will be to determine general organizations principles responsible for generating the activity patterns required for driving activity-dependent developmental processes. This work should further our understanding of the organizing principles that govern the normal development of the human nervous system, making it possible to understand the origin of neurological birth defects and to devise strategies that allow the nervous system to regenerate functioning neural circuits after injury.
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