Violet-light suppression of thermogenesis by Opsin 5 hypothalamic neurons

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.