Dual origins of the intracellular circadian calcium rhythm in the suprachiasmatic nucleus

In mammals, the master circadian clock is located in the suprachiasmatic nucleus (SCN), where most neurons show circadian rhythms of intracellular Ca(2+) levels. However, the origin of these Ca(2+) rhythms remains largely unknown. In this study, we successfully monitored the intracellular circadian Ca(2+) rhythms together with the circadian PER2 and firing rhythms in a single SCN slice ex vivo, which enabled us to explore the origins. The phase relation between the circadian PER2 and Ca(2+) rhythms, but not between the circadian PER2 and firing rhythms, was significantly altered in Cry1/Cry2 double knockout mice, which display a loss of intercellular synchronization in the SCN. In addition, in Cry1/Cry2 double knockout mice, circadian Ca(2+) rhythms were abolished in the dorsolateral SCN, but were maintained in the majority of the ventromedial SCN. These findings indicate that intracellular circadian Ca(2+) rhythms are composed of an exogenous and endogenous component involving PER2 expression.