An elucidation of hierarchy of a biological clock and a rhythm adjustment drug by generating a novel clock function-deficient mouse

内源性生物钟驱动生理和行为的振荡，周期约为24小时。当快速跨越多个时区(时差)时，我们意识到我们的内部时钟和外部明暗周期之间的不同步。虽然时差被认为是一个时间生物学问题，但其特定的分子和细胞机制尚不清楚。在这项研究中，我们表明，在V1a和V1b受体(V1a和V1b受体)遗传缺陷的小鼠中，运动活动、时钟基因表达和体温的昼夜节律迅速重新进入相移的光-暗周期。视交叉上核(SCN)脑片细胞节律的实时成像显示，V1a和V1b介导的神经元间通讯赋予SCN对外部节律扰动的内在抵抗力。药物阻断野生型小鼠SCN中的V1a和V1b可加快时差恢复的速度。

The endogenous circadian clock drives oscillations in physiology and behavior with a period of about 24 hours. When travelling rapidly across multiple time zones (jet lag), we become aware of the desynchrony between our internal clock and external light-dark cycle. Although jet lag is recognized as a chronobiological problem, its specific molecular and cellular mechanisms are poorly understood.In this study, we show that circadian rhythms of locomotor activity, clock gene expression, and body temperature rapidly re-entrained to phase-shifted light-dark cycles in mice genetically deficient in V1a and V1b receptors (V1aV1bDKO). Real-time imaging of cellular rhythms in the suprachiasmatic nucleus (SCN) slices suggested that interneuronal communication mediated by V1a and V1b confers on the SCN an intrinsic resistance to external rhythm perturbation. Pharmacological blockade of V1a and V1b in the SCN of wild-type mice accelerated the speed of recovery from jet lag.