Dissecting and modeling photic and melanopsin effects to predict sleep disturbances induced by irregular light exposure in mice

Significance Light pervasively affects physiology and behavior, especially the sleep–wake cycle (SWc), which is generated by clock signaling in the suprachiasmatic nuclei (SCN). Light synchronizes this clock and additionally exerts direct (circadian-independent) acute effects on sleep. However, it has never been clarified whether longer photic exposure, as experienced daily, might exert long-term sustained direct light effects (SDLE). Recording sleep in mice lacking a functional clock and/or the retinal photopigment melanopsin, we uncovered that circadian-driven input and SDLE equally contribute to SWc. SDLE were primarily mediated through melanopsin, with half relayed through SCN, redefining the latter’s role. Modeling allowed SWc prediction under simulated jet lags, further demonstrating SDLE as an important mechanism to consider when managing health consequences of light exposure.