Melanopsin-dependent direct photic effects are equal to clock-driven effects in shaping the nychthemeral sleep-wake cycle

Hubbard, J.; Kobayashi Frisk, M.; Ruppert, E.; Tsai, J. W.; Fuchs, F.; Robin-Choteau, L.; Husse, J.; Calvel, L.; Eichele, G.; Franken, P.; Bourgin, P.

doi:10.1101/2020.02.21.952077

bioRxiv · 10.1101/2020.02.21.952077

Melanopsin-dependent direct photic effects are equal to clock-driven effects in shaping the nychthemeral sleep-wake cycle

Hubbard, J.·Kobayashi Frisk, M.·Ruppert, E.·Tsai, J. W.·Fuchs, F.·Robin-Choteau, L.·Husse, J.·Calvel, L.·Eichele, G.·Franken, P.·Bourgin, P.

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Abstract

Nychthemeral sleep-wake cycles (SWc) are known to be generated by the circadian clock in suprachiasmatic nuclei (SCN), entrained to the light-dark cycle. Light also exerts direct acute effects on sleep and waking. However, under longer photic exposure such as the 24-hour day, the precise significance of sustained direct light effects (SDLE) and circuitry involved have been neither clarified nor quantified, as disentangling them from circadian influence is difficult. Recording sleep in mice lacking a circadian pacemaker and/or melanopsin-based phototransduction, we uncovered, contrary to prevailing assumptions, that circadian-driven input shapes only half of SWc, with SDLE being equally important. SDLE were primarily mediated (>80%) through melanopsin, of which half were relayed through SCN, independent of clock function. These findings were used for a model that predicted SWc under simulated jet-lag, and revealed SDLE as a crucial mechanism influencing behavior, and should be considered for circadian/sleep disorder management and societal lighting optimization.

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Hubbard, J., Kobayashi Frisk, M., Ruppert, E., Tsai, J. W., Fuchs, F., Robin-Choteau, L., Husse, J., Calvel, L., Eichele, G., Franken, P., Bourgin, P.. 2020-02-27. Melanopsin-dependent direct photic effects are equal to clock-driven effects in shaping the nychthemeral sleep-wake cycle. https://doi.org/10.1101/2020.02.21.952077

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