Non-canonical GABAergic Pathways in the Visual System

Light is a profoundly important regulator of physiology and behavior across a wide range of organisms. Light information is relayed from the retina to the brain via glutamate released from retinal ganglion cells (RGCs) at more than 30 brain regions, with some RGCs also co-releasing peptide transmitters. Despite the prevailing dogma that all RGCs release glutamate, there have been hints that some RGCs may be GABAergic. However, the identity and function of these potentially GABAergic RGCs is completely unknown. Our recent findings indicate that a subset of the melanopsin-expressing, intrinsically photosensitive (ip)RGCs are GABAergic. This proposal will test the overarching hypothesis that GABA release from the melanopsinexpressing, intrinsically photosensitive (ip)RGCs influences non-image forming behaviors. The aims of this proposal will define the types and targets of GABAergic RGCs and their role in visual behavior using a combination of mouse genetics, channelrhodopsin-based circuit tracing, anatomy, patch clamp electrophysiology, and behavior. In addition to mapping the identity and function of GABAergic RGCs, these studies will open up new areas of research into the role of inhibitory circuits in light-driven behavior and physiology.