The visual system remains responsive over an enormous range of ambient illumination, and this adaptation is accomplished entirely within the retina. While some of these changes in sensitivity are mediated by the rods and cones, themselves, there are also important contributions to adaptation from the other neurons in the retina. Dopamine will be the focus in the first grant period because it is thought to play a critical role in light adaptation, changing the strength of chemical and electrical synapses so that the retina remains sensitive to contrast as the intensity of the background light increases. The major targets of the dopaminergic neurons in mammals, All amacrine cells are known to be uncoupled both by dopamine and b photopic light stimulation. However, it is still uncertain which other effects of light are attributable to dopamine in mammalian retinas and what role, if any, dopamine plays in dark adaptation. Last year, the membrane properties of dopaminergic neurons were described for the first time, and they were found to fire action potentials spontaneously in vitro. Two other surprising, new findings were that, in total darkness, All amacrine cells are uncoupled and dopamine is released from the retina. These data led to the hypothesis that dopaminergic neurons are spontaneously active in total darkness, tonically inhibited in scotopic backgrounds and receive both excitatory and inhibitory input in brighter background. The goal of the proposed experiments is to test elements of this hypothesis more rigorously using computer models. It is clear that dopaminergic retinal neurons pla an important role in human vision since the electroretinogram is abnormal in patients with Parkinson's disease, in which dopaminergic neurons degenerate, and in patients taking neuroleptic drugs that block dopamine receptors. The results of these experiments may also be applicable to dopaminergic neurons elsewhere in the Central nervous system. For example, the effect of dopamine on electrical coupling was discovered in the retina and later found to occur in the brain, as well.
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