Immediate responses to ambient light in vivo reveal distinct subpopulations of suprachiasmatic VIP neurons

The circadian rhythm pacemaker, the suprachiasmatic nucleus (SCN), mediates light entrainment via vasoactive intestinal peptide (VIP) neurons (SCN(VIP)). Yet, how these neurons uniquely respond and connect to intrinsically photosensitive retinal ganglion cells (ipRGCs) expressing melanopsin (Opn4) has not been determined functionally in freely behaving animals. To address this, we first used monosynaptic tracing from SCN(VIP) neurons in mice and identified two SCN(VIP) subpopulations. Second, we recorded calcium changes in response to ambient light, at both bulk and single-cell levels, and found two unique activity patterns in response to high- and low-intensity blue light. The activity patterns of both subpopulations could be manipulated by application of an Opn4 antagonist. These results suggest that the two SCN(VIP) subpopulations connect to two types of Opn4-expressing ipRGCs, likely M1 and M2, but only one is responsive to red light. These findings have important implications for our basic understanding of non–image-forming circadian light processing.