Proposal Summary/Abstract: In the mammalian retina, there is a small subset of retinal ganglion cells (RGCs) that function as autonomous photoreceptors and exhibit light responses independent of rod/cone-driven synaptic input. These intrinsically photosensitive RGCs (known as, ipRGCs) relay light information to the brain to regulate several light-dependent processes, such as circadian photoentrainment, the pupillary light reflex (PLR), sleep, and mood. ipRGCs use the photopigment melanopsin and a G-protein coupled phototransduction cascade to respond to light, and are now known to comprise 5 different subtypes (M1-5) that can be differentiated based on morphological and electrophysiological criteria, projection targets, and transcription factor expression. Currently, there exists a major gap in our understanding of how the regulation of melanopsin and its downstream phototransduction pathways in different ipRGC subtypes govern distinct light-mediated behaviors. Based on our preliminary data, the goal of the proposed research is to determine, in Aim I, the role of melanopsin posttranslational modifications in ipRGC-mediated behaviors in vivo, and in Aim II, the phototransduction components that allow distinct ipRGC subtypes to intrinsically detect light and influence ipRGC-subtype specific behaviors. These studies will provide a critical understanding of the biochemical and molecular mechanisms by which light influences a wide range effects on human health and performance through the regulation of circadian rhythms, sleep, mood, and learning & memory.