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Circadian rhythms play an important role in many physiological processes. We have previously reported that no periodic fluctuation in the Bmal1 mRNA is observed in the liver of the chipmunk, a mammalian hibernator, in the hibernation season, suggesting that peripheral circadian clocks are not functional during hibernation. In contrast, the Per2 mRNA levels are transiently increased by elevated body temperature during interbout arousal and showed periodic fluctuations in the hibernation season, suggesting that periodic expression of the Per2 mRNA may be restored during interbout arousal. In the present study, we analyzed Per1 gene expression in the chipmunk liver. The Per1 mRNA showed circadian fluctuations with a peak during the late sleep period in the non-hibernation season and periodic fluctuations with a peak during the early interbout arousal in the hibernation season. In both the non-hibernation and hibernation seasons, Per1 gene expression was phase-advanced relative to Per2 gene expression, and the phase relationship between the two genes was maintained, suggesting that for some genes, periodic gene expression, similar to circadian expression in the non-hibernation season, may be restored during interbout arousal. Interestingly, Per1 gene transcription was differentially activated by BMAL1 in the non-hibernation season and possibly by CREB1 in the hibernation season., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

During winter hibernation, a diverse range of small mammals can enter prolonged torpor. They spend the nonhibernation season as a homeotherm but the hibernation season as a heterotherm. In the hibernation season, chipmunks (Tamias asiaticus) cycle regularly between 5 and 6 days-long deep torpor with a body temperature (Tb) of 5 to 7 °C and interbout arousal of ∼20 h, during which, their Tb returns to the normothermic level. Here, we investigated Per2 expression in the liver to elucidate the regulation of the peripheral circadian clock in a mammalian hibernator. In the nonhibernation season, as in mice, heat shock factor 1, activated by elevated Tb during the wake period, activated Per2 transcription in the liver, which contributed to synchronizing the peripheral circadian clock to the Tb rhythm. In the hibernation season, we determined that the Per2 mRNA was at low levels during deep torpor, but Per2 transcription was transiently activated by heat shock factor 1, which was activated by elevated Tb during interbout arousal. Nevertheless, we found that the mRNA from the core clock gene Bmal1 exhibited arrhythmic expression during interbout arousal. Since circadian rhythmicity is dependent on negative feedback loops involving the clock genes, these results suggest that the peripheral circadian clock in the liver is nonfunctional in the hibernation season., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

The serotonin (5-HT) system in the brain is a global modulator thought to tune up a unique subset of brain keynotes such as emotion, motivation, and sleep/conscious states in the deepest seats of cognition and behavior. In pursuit for coherent accounts of such higher-order issues, we have been trying to deduce the system dynamics of 5-HT in full span from the perturbation-response couples elicited by our most quick, specific, extensive, and reversible depletion of the brain 5-HT so far available via plasma precursor annihilation by injection of a tryptophan degrading enzyme (TSO) (ISTRY meetings-1986 in Cardiff, -92 in Nagoya and -98 in Hamburg). Herein discussed are the dynamics of the 5-HT depletion both in the whole brain and regional dimensions, and then the perturbation-induced manifestation of a continuous behavioral quiescence underlain by chaotic patterns of sleep/waking states. This response in sharp contrast to those by earlier serotonin depletors, prompts us to consider a serious revision of the current 5-HT scenario. In the light of our research, future directions will be discussed together with the RTD (rapid tryptophan depletion) claiming the impaired brain 5-HT turnover by a partial decline of plasma tryptophan.