ipRGC properties prevent light from shifting the SCN clock during daytime.

The suprachiasmatic nucleus (SCN), the central circadian pacemaker, receives photic input exclusively from intrinsically photosensitive retinal ganglion cells (ipRGCs)1,2. However, light mainly shifts the SCN clock during night-time3-5. Here we induced phase shifts in the SCN clock during the daytime in mice by activating ipRGCs using chemogenetics or violet light. Our data reveal that the inability to induce daytime shifts with light in most animals is not only attributed to the SCN, as has been proposed for decades, but also requires the limitation of ipRGC firing via depolarization block. Chemogenetic activation of ipRGCs induces large shifts during both night-time and daytime, but daytime shifts require brain circuits and neuropeptide transmitters that are dispensable for night-time shifts. Thus, propensity of ipRGCs for depolarization block not only prevents daytime shifts in mice, but also limits the magnitude of night-time shifts, suggesting that ipRGC inputs to SCN act as an integrated pacemaker across the circadian cycle.