Regulation of Retinal Functions by Light and a Circadian Clock

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It is still unclear how the combination of an internal clock and environmental light regulate the well-known daily circadian changes in activity of both vertebrate and invertebrate animals. Molecular mechanisms are being discovered in many laboratories, but little is known about the biochemical and physiological mechanisms in the eye and brain. Clock function prepares the photoreceptors in the retina of the eye to function optimally in different backgrounds of daylight, dusk, or night; in turn, visual input from the eyes help modulate the correct timing of the running clock in the brain. This project uses the horseshoe crab, Limulus, as a model system that is amenable to extensive biochemical analysis. Molecular, biochemical and immunochemical approaches are used to see how the clock may produce and modulate (phosphorylated) particular proteins in the retina. One protein in the photoreceptors is known to have both structural and enzyme properties, and experiments test how its functions are modulated by the clock input from the brain to the eye. The biochemical nature of how the clock input to the eye can prime the photoreceptor response to light is studied by testing the role of the clock and the role of light in driving gene expression in the eye, separately or in combination. These studies will provide new insights into the biochemical processes underlying the day-to-night changes in the retina that are critical for normal vision. The impact extends beyond visual neuroscience to the analysis of circadian behavior, and potentially to how human daily cyclic activity may be modulated.