Abitbol Karine, Debiesse Ségolène, Molino François, Mesirca Pietro, Bidaud Isabelle, Minami Yoichi, Mangoni Matteo E, Yagita Kazuhiro, Mollard Patrice, Bonnefont Xavier
Institut de Génomique Fonctionnelle, CNRS, INSERM, Montpellier, France.
Laboratoire Charles Coulomb, Université de Montpellier, CNRS UMR 5221, Montpellier, France.
PLoS One. 2017 Oct 23;12(10):e0187001. doi: 10.1371/journal.pone.0187001. eCollection 2017.
Circadian clocks drive biological rhythms with a period of approximately 24 hours and keep in time with the outside world through daily resetting by environmental cues. While this external entrainment has been extensively investigated in the suprachiasmatic nuclei (SCN), the role of internal systemic rhythms, including daily fluctuations in core temperature or circulating hormones remains debated. Here, we show that lactating mice, which exhibit dampened systemic rhythms, possess normal molecular clockwork but impaired rhythms in both heat shock response gene expression and electrophysiological output in their SCN. This suggests that body rhythms regulate SCN activity downstream of the clock. Mathematical modeling predicts that systemic feedback upon the SCN functions as an internal oscillator that accounts for in vivo and ex vivo observations. Thus we are able to propose a new bottom-up hierarchical organization of circadian timekeeping in mammals, based on the interaction in the SCN between clock-dependent and system-driven oscillators.
昼夜节律时钟驱动着周期约为24小时的生物节律，并通过环境线索的每日重置与外界保持同步。虽然这种外部同步在视交叉上核（SCN）中已得到广泛研究，但包括核心体温或循环激素的每日波动在内的内部系统节律的作用仍存在争议。在这里，我们表明，表现出减弱的系统节律的哺乳期小鼠具有正常的分子时钟机制，但它们的SCN中热休克反应基因表达和电生理输出的节律受损。这表明身体节律在时钟下游调节SCN活动。数学建模预测，SCN上的系统反馈作为一个内部振荡器，解释了体内和体外观察结果。因此，我们能够基于时钟依赖性振荡器和系统驱动振荡器在SCN中的相互作用，提出一种新的哺乳动物昼夜计时的自下而上的层次组织。
