Differential roles of AVP and VIP signaling in the postnatal changes of neural networks for coherent circadian rhythms in the SCN

The suprachiasmatic nucleus (SCN) is the site of the master circadian clock in mammals. The SCN neural network plays a critical role in expressing the tissue-level circadian rhythm. Previously, we demonstrated postnatal changes in the SCN network in mice, in which the clock gene products CRYPTOCHROMES (CRYs) are involved. Here, we show that vasoactive intestinal polypeptide (VIP) signaling is essential for the tissue-level circadian PER2::LUC rhythm in the neonatal SCN of CRY double-deficient mice (Cry1,2(−/−)). VIP and arginine vasopressin (AVP) signaling showed redundancy in expressing the tissue-level circadian rhythm in the SCN. AVP synthesis was significantly attenuated in the Cry1,2(−/−) SCN, which contributes to aperiodicity in the adult mice together with an attenuation of VIP signaling as a natural process of ontogeny. The SCN network consists of multiple clusters of cellular circadian rhythms that are differentially integrated by AVP and VIP signaling, depending on the postnatal period.