Entrainment of circadian rhythms depends on firing rates and neuropeptide release of VIP SCN neurons

The mammalian suprachiasmatic nucleus (SCN) functions as a master circadian pacemaker, integrating environmental input to align physiological and behavioral rhythms to local time cues. Approximately 10% of SCN neurons express vasoactive intestinal polypeptide (VIP); however, it is unknown how firing activity of VIP neurons releases VIP to entrain circadian rhythms. To identify physiologically relevant firing patterns, we optically tagged VIP neurons and characterized spontaneous firing over three days. VIP neurons had circadian rhythms in firing rate and exhibited two classes of instantaneous firing activity. We next tested whether physiologically relevant firing affected circadian rhythms through VIP release. We found that VIP neuron stimulation with high, but not low, frequencies shifted gene expression rhythms in vitro through VIP signaling. In vivo, high frequency VIP neuron activation rapidly entrained circadian locomotor rhythms. Thus, increases in VIP neuronal firing frequency release VIP and entrain molecular and behavioral circadian rhythms.\n\nHighlightsO_LIMazuski et al. identified three classes of circadian SCN neurons based on their distinct firing patterns consistent over multiple days\nC_LIO_LIThere are two distinct classes (tonic and irregular firing) of VIP SCN neurons.\nC_LIO_LIStimulation of VIP SCN neurons at physiologically relevant frequencies phase shifts whole-SCN circadian rhythms in gene expression through VIP release. These effects are blocked with VIP antagonists.\nC_LIO_LIFiring of VIP SCN neurons entrains circadian rhythms in locomotor behavior in a frequency and time-of-day dependent manner.\nC_LI