Published at Neuron, Oct 2021.
doi.org/10.1016/j.neuron.2021.07.026
The suprachiasmatic nucleus (SCN) is the master circadian pacemaker in mammals and is entrained by environmental light. However, the molecular basis of the response of the SCN to light is not fully understood. We used RNA/Chromatin Immunoprecipitation/single-nucleus sequencing with circadian behavioral assays to identify mouse SCN cell types and to explore their responses to light. We identified three peptidergic cell types that responded to light in the SCN: (arginine vasopressin [AVP], vasoactive intestinal peptide [VIP], and cholecystokinin [CCK]). In each cell type, light-responsive subgroups were enriched for expression of Neuronal PAS Domain Protein 4 (NPAS4) target genes. Further, mice lacking Npas4 had a longer circadian period in constant conditions, a damped phase response curve to light, and reduced light-induced gene expression in the SCN. Together, our data indicate that NPAS4 is necessary for normal transcriptional responses to light in the SCN and is critical for photic phase-shifting of circadian behavior.