CIRCADIAN AND EFFERENT MODULATION OF VISUAL SENSITIVITY

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DESCRIPTION (from the author's abstract): Circadian and efferent modulation of visual sensitivity is the main focus of this project. Circadian clocks in the Limulus brain and Japanese quail eye modulate retinal structure and function in both animals, and clock(s) in the eye and/or brain modulate visual sensitivity in humans. Non circadian efferent input from the brain further modulates the quail retina, and changes in blood glucose further influence human visual sensitivity. Our long range goal is to understand how these modulatory factors adapt vision for essential tasks. This project has three interrelated lines of research with Specific Aims to investigate: 1) circadian modulation of photoreceptor noise by rhodopsin stabilization; 2) circadian modulation of retinal sensitivity by dopamine and melatonin; 3) circadian and metabolic modulation of human vision. The PI proposes to study the circadian modulation of photoreceptor noise by analyzing rhodopsin stabilization in Limulus with a range of techniques including voltage clamp, site-specific mutagenesis, gene expression in Xenopus oocytes and Drosophila eyes. The PI will study the circadian modulation of retinal sensitivity by the putative transmitters dopamine and melatonin in Japanese quail using in situ hybridization , nuclear run-on assays, Rnase protection assays and other cell and molecular biological techniques. We will study the circadian and metabolic modulation of vision in humans of various ages and diabetic conditions using psycho physical methods and FMRI of the visual cortex. The primary tenet of this project is that comprehensive studies of human vision and two suitable animal models will yield new insights on how circadian mechanisms modulate visual sensitivity. These studies may shed light on a possible relationship between photoreceptor noise, circadian rhythms and some forms of degenerative retinal disease.