Frequency-modulated timer regulates torpor-arousal cycles during hibernation in distinct small mammalian hibernators

Hibernation allows mammals to endure harsh seasons by reducing their basal metabolism and body temperature (Tb) to minimize energy expenditure. During hibernation in small animals such as Syrian hamsters and 13-lined ground squirrels, Tb decreases to an ambient level ( < 5 °C) and remains constant for days to weeks in a physiological condition termed deep torpor. Torpor is interrupted by periods of arousal, during which Tb recovers to a euthermic level (approximately 37 °C), and these torpor-arousal cycles are repeated multiple times during hibernation. However, little is known about the mechanisms governing Tb fluctuations during hibernation. In this study, we employed an unbiased model selection approach to Tb data and revealed that a model incorporating frequency modulation quantitatively reproduced Tb fluctuation during hibernation in Syrian hamsters. We found that an unexpectedly long period of 120-430 days modulates a shorter period of several days. In addition, the aforementioned model reproduced Tb fluctuation in 13-lined ground squirrels, which can undergo repeated hibernation according to intrinsic circannual rhythms in constant laboratory conditions. This is the first quantitative study to demonstrate the concerted action of two endogenous periods, one lasting a few days and the other lasting a year, in the torpor-arousal cycles of distinct mammalian hibernators. We anticipate that our theoretical analysis of Tb fluctuation will be a starting point for quantitative comparisons of hibernation patterns across various hibernating species. Furthermore, quantification of Tb data using models will foster our understanding of the molecular mechanisms of hibernation by revealing the biological processes operating within these periods.