Subcellular Origins of Extensive Spatial Integration by Ganglion Cell Photoreceptors

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PROJECT SUMMARY/ABSTRACT When faced with a visual scene, the brain encodes both image detail and the scene’s overall intensity, measured as irradiance. Encoding irradiance is critical for circadian regulation, pupil constriction, and image vision, among other important functions. A canonical feature of irradiance encoding is the blurring of image detail in favor of extensive spatial integration of light. The cells in the retina that transmit irradiance information to the brain are the intrinsically photosensitive retinal ganglion cells (ipRGCs). My goal is to understand how the mechanisms of phototransduction in the ipRGCs support this spatial integration. Melanopsin, the light- sensitive protein in ipRGCs, is distributed throughout the dendrites, soma, and axon. IpRGCs send irradiance information to the brain using spikes and phototransduction within the axon is likely to shape spike output. Preliminary experiments indicate that ipRGC axons are indeed photosensitive. In mice, melanopsin immunostaining labels axons, including at the optic disk. In electrophysiological recordings of mouse ipRGCs, illumination of the axon evokes spiking responses, and the cells are more sensitive to large stimuli that illuminate their axons in addition to their somas and dendrites. I hypothesize that phototransduction in the axon enables the spatial integration of light over an unexpectedly large area. The lab has established protocols for electrophysiological recordings from the soma and axon of ipRGCs, and for imaging visually-evoked Ca2+ dynamics in the population of ipRGC axon terminals. I propose an investigation into mechanisms of axonal photosensitivity (Aim 1) and the axonal contribution to spatial integration at the level of the cell population (Aim 2). To complement my investigations in the mouse, I will also measure the properties of ipRGCs in a species that has larger eyes and thus longer axons. My proposed experiments will provide an understanding of how signal transduction operates in distinct cellular compartments of a sensory neuron to support spatial integration.