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

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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.