Melanopsin contributes to circadian photic responses in mice in a sex-dependent manner

Proper entrainment of the body's circadian rhythms to the environment is critical to human health. Light is one of the strongest cues driving circadian photoentrainment of the central circadian pacemaker, the suprachiasmatic nucleus (SCN), via projections from the melanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs). Circadian research has historically centered males, and recent work has revealed multiple sex-differences in circadian circuitry and function, indicating that our understanding of this system in females is severely limited. Moreover, while recent studies have investigated the role of hormonal modulation of light responses, the additional possibility that ipRGC inputs may also be sex-dependent has not been directly tested. Here, we report that not only do ipRGCs in female mice show higher levels of melanopsin expression, but that melanopsin also plays a larger role in shaping circadian photic responses in females compared to males. Collectively, these results define a new retinal source for sex-dependent differences in circadian behavior.