Cholecystokinin neurons in mouse suprachiasmatic nucleus regulate the robustness of circadian clock

The suprachiasmatic nucleus (SCN) can generate robust circadian behaviors in mammals under different environments, but the underlying neural mechanisms remained unclear. Here, we showed that the activities of cholecystokinin (CCK) neurons in the mouse SCN preceded the onset of behavioral activities under different photoperiods. CCK-neuron-deficient mice displayed shortened free-running periods, failed to compress their activities under a long photoperiod, and developed rapid splitting or became arrhythmic under constant light. Furthermore, unlike vasoactive intestinal polypeptide (VIP) neurons, CCK neurons are not directly light sensitive, but their activation can elicit phase advance and counter light-induced phase delay mediated by VIP neurons. Under long photoperiods, the impact of CCK neurons on SCN dominates over that of VIP neurons. Finally, we found that the slow-responding CCK neurons control the rate of recovery during jet lag. Together, our results demonstrated that SCN CCK neurons are crucial for the robustness and plasticity of the mammalian circadian clock. [Display omitted] •Activities of SCN CCK neurons track the onset of circadian behavioral activities•SCN CCK neurons coordinate the circadian activities under long photoperiods•SCN CCK neurons interact with VIP neurons in the light entrainment pathway•SCN CCK neurons regulate the recovery rate of jet lag The mouse central circadian clock residing in the SCN consists of multiple neuronal subtypes. Xie et al. uncover a neural circuit involving CCK neurons that times the onset of circadian activities and regulates circadian behaviors under a long-day photoperiod and phase shift in jet lag.