The opsin family of G-protein coupled receptors are employed as light detectors in animals. Opsin 5 (neuropsin, OPN5) is a highly conserved, violet light (380 nm λ max ) sensitive opsin 1 , 2 . In mice, OPN5 is a known photoreceptor in retina 3 and skin 4 but is also expressed in the hypothalamic preoptic area (POA) 5 . Here we describe a light-sensing pathway in which Opn5 expressing POA neurons regulate brown adipose tissue (BAT) thermogenesis. We show Opn5 expression in glutamatergic warm-sensing POA neurons that receive synaptic input from multiple thermoregulatory nuclei. We further show that Opn5 POA neurons project to BAT and decrease its activity under chemogenetic stimulation. Opn5 null mice show overactive BAT, elevated body temperature, and exaggerated thermogenesis when cold challenged. Moreover, violet photostimulation during cold exposure acutely suppresses BAT temperature in wild-type, but not in Opn5 null mice. Direct measurements of intracellular cAMP ex vivo reveal that Opn5 POA neurons increase cAMP when stimulated with violet light. This analysis thus identifies a violet light sensitive deep brain photoreceptor that normally suppresses BAT thermogenesis.

Highlights d Adipocytes express encephalopsin (OPN3), a 480 nm bluelight-sensitive opsin d Mice lacking OPN3 or blue light have diminished thermogenesis during cold exposure d Loss of OPN3 reduces oxygen consumption and energy expenditure d White adipocyte OPN3 promotes lipolysis during cold exposure

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Obtaining a parts list of the sensory components of the retina is vital to understand the effects of light in behavior, health, and disease. Rods, cones, and intrinsically photosensitive retinal ganglion cells (ipRGCs) are the best described photoreceptors in the mammalian retina, but recent functional roles have been proposed for retinal neuropsin (Opn5)-an atypical opsin. However, little is known about the pattern of Opn5 expression in the retina. Using cre (Opn5 cre ) and cre-dependent reporters, we uncover patterns of Opn5 expression and find that Opn5 is restricted to retinal ganglion cells (RGCs). Opn5-RGCs are nonhomogenously distributed through the retina, with greater densities of cells located in the dorsotemporal quadrant. In addition to the local topology of these cells, using cre-dependent AAV viral tracing, we surveyed their central targets and found that they are biased towards image-forming and image-stabilizing regions. Finally, molecular and electrophysiological profiling reveal that Opn5-RGCs comprise previously defined RGC types that respond optimally to edges and objectmotion (F-mini-ONs, HD2, HD1, LEDs, ooDSRGCs, etc.). Together, these data describe the second collection of RGCs that express atypical opsins in the mouse, and expand the roles of image-forming cells in retinal physiology and function. INTRODUCTIONRetinal ganglion cells (RGCs) comprise a diverse collection of 45 or more projection neuron types that link retinal events, such as theThis is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.