This research project is an experimental study that seeks to understand how neuronal networks change or adapt to changes in environmental stimulation. In the fish retina, the light-evoked responses of cone horizontal cells, a type of second order cell that receives synaptic contact from cones, depend on the ambient illumination and on a circadian clock. A circadian clock is a type of biological oscillator that has persistent rhythmicity with a period of approximately 24 hours in the absence of external timing cues (e.g. constant darkness). In addition, a circadian clock can be entrained by cyclic environmental stimuli, such as light. Following dark adaptation, red cone input to cone horizontal cells predominates during the daytime and rod input predominates during the nighttime. Because these effects are observed in fish maintained in constant darkness and because prior reversal of the light/dark cycle reverses the effects, it can be concluded that a circadian clock regulates the effects of dark adaptation. However, the circadian factors that regulate the effects of dark adaptation on cone horizontal cells are not known, nor are the factors that entrain the clock following reversal of the light/dark cycle. Accordingly, a combination of electrophysiological, neurochemical and anatomical techniques will be used to investigate circadian rhythmic regulation of the effects of dark adaptation in the goldfish retina. It will be determined whether a circadian clock regulates cone horizontal cell coupling, as well as whether there are circadian rhythms in the levels of the retinal neurotransmitters, dopamine and melatonin, and/or in extracellular pH. It will also be determined whether the circadian rhythm in horizontal cell light responses depends on rhythms of dopamine and melatonin, as well as on a rhythm of extracellular pH. Finally, it will be determined whether dopamine is involved in entrainment of the clock. The membrane potential, light-evoked responses and electrical and dye coupling of cone horizontal cells will be studied under conditions of constant darkness, using a superfused, intact retina preparation. Disruption of circadian clock processes in the retina may mediate photoreceptor cell degeneration. Thus, increased understanding of circadian clock processes and pathways and of transmitter function will aid in the understanding of human retinal processes and dysfunction, as well as provide the basis for drug therapy for retinal disorders. In addition, increased knowledge of the action of dopamine in the retina may aid in the understanding and treatment of Parkinson's disease.
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