Genetic dissection of the role of ganglion cell photoreceptors in vision

In mammals, all light information is relayed to the brain by the retina. For decades, the rods and cones were thought to be the sole source of retinal photosensitivity. Recently, however, researchers uncovered a unique population of atypical retinal ganglion cells (RGC) in the inner retina that are intrinsically photosensitive (ipRGCs) due to expression of the photopigment melanopsin1,2. ipRGCs were initially thought to be involved only in subconscious visual behaviors such as circadian photoentrainment and the pupillary light reflex3. However, my postdoctoral work demonstrated an unexpected, but important role for ipRGCs in pattern vision, showing that animals lacking melanopsin signaling or subsets of ipRGCs have deficits in contrast sensitivity4. These results force us to reconsider the role of ipRGCs in behavior. The mechanisms underlying this function of melanopsin and ipRGCs in contrast sensitivity are currently completely unknown. The major goal of my laboratory, and the work for which funds from The Karl Kirchgessner Foundation will be used, is to define the subtypes, connectivity, and mechanisms through which ipRGCs influence behavior. The experiments we will undertake to achieve this ambitious goal are outlined in the aims below.