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, electrophysiology and modeling are proposed to investigate the mechanisms of intercellular coupling that underlie the propagation of retinal waves. In addition, pharmacological manipulations that significantly alter the correlated firing patterns induced by retinal waves and transgenic mice lacking retinal waves will be used to investigate their role in the development of retinal projections to the lateral geniculate nucleus. One result of this work will be to determine the critical parameters of the activity patterns generated by retinal waves for driving activity dependent developmental processes. This work will test the hypothesis that spontaneous, correlated activity is responsible for proper organization of synapses in the developing nervous system and will lead to a further understanding of the cellular and molecular basis for activity-dependent processes in the developing visual system. 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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