Cross-talk between ganglion-cell photoreceptors and other neurons in the retina

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DESCRIPTION (provided by applicant): One function of the visual system is to enable conscious visual perception of details in the environment; this requires the rod and cone photoreceptor cells in the retina. The visual system also mediates subconscious photic regulation of various physiological functions such as resetting of our body clocks to the solar cycle. Failure to reset these clocks results in "jet lag" symptoms which can have serious health consequences including sleep disorders and cancer. Subconscious photoreception requires not only rods and cones but also the recently discovered ganglion-cell photoreceptors, i.e. the intrinsically photosensitive retinal ganglion cells (ipRGCs). ipRGCs interact bidirectionally with rod/cone-driven bipolar-cell and amacrine-cell circuits. This proposal uses electrophysiological and imaging methods to study such interactions in rodent retinas and comprises three goals: (1) To characterize the functions and morphologies of bipolar and amacrine cells innervating the ipRGCs, through dual intracellular recordings from a bipolar/amacrine cell and an ipRGC followed by fluorescence imaging of dyes injected into these cells; (2) To examine the influence of dopamine and other amacrine-cell neuromodulators on ipRGC light responses by analyzing the effects of receptor agonists and antagonists; and (3) To investigate which bipolar and amacrine cell types receive synaptic inputs from ipRGCs, through dual intracellular recordings followed by fluorescence imaging. Findings from these studies will enable a better understanding of how rod/cone signals regulate our body clocks, and will also provide clues as to how the ipRGCs may modulate rod/cone circuits and thus conscious visual perception. LAY SUMMARY: Neuronal circuits for conscious vision and for subconscious visual functions (e.g. regulation of sleep timing) interact in the retina. This proposal will study the functional roles of such interactions and may help design better therapies and workplace policies combating or preventing jet lag problems. CANDIDATE: My #1 career goal is to get a faculty position and continue to explore neuronal mechanisms for both conscious and subconscious vision. This K99/R00 award will help me achieve this goal, since I will learn imaging and anatomical techniques from my sponsor, and the award topic is highly relevant to my long-term research interests and will be a basis for future ROVs. The excellent research facilities and mentor support at Brown University will greatly facilitate execution of the planned experiments.