FBS Colloquia No.159Synaptic Plasticity Group

Molecular and neuronal signaling in the suprachiasmatic nucleus underlying the robustness of circadian rhythm: mice deficient in vasopressin V1a and V1b receptors are resistant to jet lag

The endogenous circadian clock drives oscillations in physiology and behavior with a period of about 24 hours. We are not usually aware of this system because it is completely synchronized with environmental light-dark cycle, but travelling rapidly across multiple time zones suddenly makes us aware of the desynchrony, causing sleep disturbances and gastrointestinal distress. Repeated jet-lag exposure and rotating shift work increase the risk of lifestyle-related diseases, such as cardiovascular complaints and metabolic insufficiency. Although jet lag is recognized as a chronobiological problem, its specific molecular and cellular mechanisms are poorly understood. Here, I show that circadian rhythms of locomotor activity, clock gene expression, and body temperature rapidly re-entrained to phase-shifted light-dark cycle in mice genetically deficient in V1a and V1b receptors (V1aV1bDKO). Nevertheless, the behavior of V1aV1bDKO mice was still coupled to the internal clock, which oscillated normally under standard conditions. Response to a light pulse was also normal in V1aV1bDKO mice. 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, which elicits vasopressin signaling as a potential pharmaceutical intervention for management of circadian rhythm misalignment, such as jet lag and shift work.
(Ref. Yamaguchi et al., Science, 342: 85-90, 2013)