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

Ryosuke Enoki,Shigeru Kuroda,Sato Honma,Ken-ichi Honma,Daisuke Ono

doi:10.1038/srep41733

Ryosuke Enoki, Shigeru Kuroda + Show 3 more

Open Access

https://doi.org/10.1038/srep41733

Copy DOI

Abstract

In mammals, the master circadian clock is located in the suprachiasmatic nucleus (SCN), where most neurons show circadian rhythms of intracellular Ca2+ levels. However, the origin of these Ca2+ rhythms remains largely unknown. In this study, we successfully monitored the intracellular circadian Ca2+ 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 Ca2+ 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 Ca2+ rhythms were abolished in the dorsolateral SCN, but were maintained in the majority of the ventromedial SCN. These findings indicate that intracellular circadian Ca2+ rhythms are composed of an exogenous and endogenous component involving PER2 expression.

Highlights

Expression in the suprachiasmatic nucleus (SCN) up to at latest postnatal day 14 but afterwards they lose the circadian rhythm because of a dysfunction of the neural network[14,15]
The phase relationships between these circadian rhythms were substantially changed in the Cry1,2−/− SCN
These findings indicate that the circadian Ca2+ rhythm is dissociable from the core loop and has dual origins: one of exogenous origin, the circadian input from the SCN network, and the other of endogenous origin, the intracellular circadian oscillation

Summary

Introduction

Expression in the SCN up to at latest postnatal day 14 but afterwards they lose the circadian rhythm because of a dysfunction of the neural network[14,15]. We found that the circadian Ca2+ rhythms were abolished in the dorsolateral region of the SCN; the rhythm was maintained in the ventromedial region of the SCN in Cry1,2−/− mice. These findings indicate that intracellular circadian Ca2+ rhythms are determined by at least two factors: the endogenous component from the core loop and the exogenous component from the SCN neural network

Methods

Results

Conclusion