The goal of this research program is to further our understanding of the developmental maturation of functional networks in the vertebrate retina, and to investigate the signaling cascades that direct and control this maturation. In particular, we propose to test the thesis that neural activity is a signal that helps sculpt intricate, mature circuits in the retina from initially imprecise neuronal connections. To achieve this goal, first, the maturation of the retinal network in the peripheral growth zone of the fish retina will be characterized. In this zone, at the rim of the mature tissue, new retina develops continuously in a process similar, if not identical, to embryological development. Fish offer an experimental model accessible to manipulations not readily possible in the mammalian eye. To characterize circuitry maturation, the electrophysiological properties of ganglion cells, the output neuron of the retina, will be investigated. Developmental changes in both the intrinsic properties of individual ganglion cells and in the retinal network reflected, in turn, in ganglion cell function will be studied. Maturation of neural circuits will be studied through measurements of the spiking activity of developing ganglion cells. The neural networks formed after photoreceptors have matured will be investigated by characterizing the development of the functional properties of light-driven networks. Maturation of the intrinsic electrophysiological properties of developing ganglion cells will be studied through measurements of the biophysical and pharmacological properties of ligand-gated membrane currents in single cells. After defining the features of network maturation, we will assess the role of neural activity as a modulator of maturation by testing the effects on network maturation of blocking specific synaptic activity-dependent signaling pathways.
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