This project seeks to understand how neuronal circuits in the rabbit retina change or adapt due to a circadian oscillator. A circadian clock or oscillator has a rhythmicity of approximately 24 hours in the absence of external timing cues. Cyclic environmental stimuli such as light can entrain the circadian clock. This project will determine whether a circadian clock regulates cone-horizontal cells that exhibit a diurnal rhythm. The dominant photoreceptor input to dark-adapted, cone horizontal cells exhibits a diurnal rhythm; cone inputs predominate during the day and rod inputs predominate during the night. A combination of electrophysiological, neurochemical and anatomical techniques will be utilized to determine whether a circadian clock is involved in horizontal cell and ganglion cell light responsiveness, as well as horizontal cell gap junctional coupling. It will be determined whether a circadian clock controls the levels of dopamine, melatonin and adenosine, as well as extracellular pH. It will then be determined whether the circadian clock uses any of these signaling mechanisms to regulate the light responses of horizontal and ganglion cells. Measurements will be made in constant darkness (absence of timing cues) in a superfused, retinal eyecup preparation. Disruption of the circadian clock may result in retinal photoreceptor degeneration. Thus, increased understanding of the circadian clock processes will aid in the understanding of human retinal processes and dysfunction. These studies may also provide the basis for drug therapy for retinal disorders thought to be linked to the disruption of circadian processes.
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