title: [Molecular and Neural Mechanisms for the Robustness of the Circadian Clock].
abstract: The endogenous circadian clock drives robust oscillations in physiology and behavior, such as hormone secretions and sleep/wake cycles, with a period of about 24 h. We are rarely aware of this internal clock system because it is usually synchronized with environmental light-dark cycles. However, travelling rapidly across multiple time zones in a jet airplane suddenly makes us aware of the desynchrony between the body clock and external time, causing sleep disturbances and gastrointestinal problems. Although jet lag is recognized as a chronobiological problem, its specific molecular and neural mechanisms are poorly understood. To address this issue, we identified genes highly expressed in the suprachiasmatic nucleus of the anterior hypothalamus (SCN), the mammalian master clock that controls rhythmic behavior, then analyzed the behavior of knock-out mice for these genes under jet lag condition. We found that the circadian rhythms of locomotor activity and clock gene expression rapidly re-entrained to phase-shifted light-dark cycles in mice genetically deficient in V1a and V1b receptors. Real-time imaging of cellular rhythms in the SCN suggested that interneuronal communication through V1a and V1b confers on the SCN an intrinsic resistance to external perturbation, enhancing the robustness of the SCN clockwork. Pharmacological blockade of V1a and V1b in the SCN of wild-type mice accelerated their recovery from jet lag symptoms, suggesting vasopressin signaling as a potential pharmaceutical intervention for the management of circadian rhythm misalignment.
authors.affiliation: Department of Systems Biology, Graduate School of Pharmaceutical Sciences, Kyoto University.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Yamaguchi
mesh_terms: D000818:Animals; D057906:Circadian Clocks / Q000235:genetics / Q000502:physiology*; D020179:Jet Lag Syndrome / Q000503:physiopathology; D051379:Mice; D018345:Mice, Knockout; D013493:Suprachiasmatic Nucleus / Q000502:physiology