The long-term objective of the proposed research is to understand what processes contribute to the development of image information processing in the retinas of embryos and neonatal animals. This basic research could have important implications for future cure of genetic diseases of the retina. To achieve the objectives of the research, a theoretical framework was proposed, which shows how dendritic growth, light exposure, and spontaneous waves of activity (common to immature isolated retinas, but as yet not studied in vivo) can contribute to the development of retinal information processing. The specific questions being asked are: 1) Do developing retinas have spontaneous waves of activity in vivo? If so, what are the properties of this activity? To answer these questions, the eyes of developing turtles will be recorded with two electrodes simultaneously and the results analyzed with a new mathematical technique. The experiments will be performed under normal conditions and visually- and pharmacologically-abnormal ones. The data will then be compared to computer simulations performed with the theoretical framework. 2) Are spontaneous waves mediated by extracellular potassium and cholinergic synapses? To answer this question, a new technique for optically imaging Ca2+ in ganglion cells will be used. This technique will allow to obtain the waves' spatio-temporal profile across cells and thus, to test the predictions made by a recent model of these waves. In particular, this model predicts the effects of neostigmine, a cholinesterase inhibitor, Cs+ and TEA, two K+-currents blockers, and Co2+, a synaptic blocker. 3) Does spontaneous activity contribute to the development of receptive- field size and orientation selectivity? To test whether waves contribute to the development of these properties, a technique to implant intraocularly a piece of polymer that slowly releases drugs mixed with it was developed. In the proposed experiments, the drugs will be neostigmine and Co2+. Incidence of orientation selectivity and receptive-field size will be measured for each of these conditions as a function of age, and the results compared to those of new computer simulations.
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