(From the Applicant?s Abstract): The primary focus of this proposal is to gain expertise in the field of visual neuroscience by studying cones. The ability of cones to adapt over wide ranges of illumination is essential for normal visual function. Critical for maintaining this property of cones is to deactivate the G-protein coupled signal transduction cascade that mediates cone responses, I propose a strategy to examine cone adaptation in Xenopus. Specifically, I propose to: Analyze light adaptation of short wavelength violet cones. Investigate the molecular mechanism underlying the adaptation response by specifically altering cone arrestin levels in violet cones. By combining electrophysiological and behavioral approaches with molecular biology in a cone-rich experimental model, Xenopus, I hope to understand how cones regulate and maintain their sensitivity. Mutations in photoreceptor specific genes are known to cause retinal diseases such as retinitis pigmentosa, Oguchi?s disease and rod-cone dystrophy. Although the visual effects of cone arrestin mutations are not known, its location on the X chromosome makes it a prime candidate for X-linked retinopathies and recessive cone dystrophy. My training program will focus on analyzing the functional effects of cone arrestin mutations in the retina.
