Generalized harmonic analysis reveals a frequency modulated timer regulates mammalian hibernation

Mammalian hibernators decrease basal metabolism and body temperature (Tb) to minimize energy expenditure in harsh seasons. During hibernation, Tb drops to low temperature (<10 °C) and remains constant for days, known as deep torpor. Spontaneous interbout arousals interrupt torpor bouts, when Tb recovers to euthermic state ~37 °C. Torpor-interbout arousal event repeats during hibernation. Little is known about mechanisms governing Tb fluctuation during hibernation. Here, we analyzed Tb fluctuation across Syrian hamsters′ hibernation cycle using generalized harmonic analysis and discovered a model with frequency modulation quantitatively reproducing Tb fluctuation. This analysis identified that an unexpectedly longer period of 120—430 days modulates period of several days, generating Tb fluctuation. We propose that concerted action of two endogenous periods governs torpor-interbout arousal cycles during hibernation.

An hourglass mechanism controls torpor bout length in hibernating garden dormice

Hibernating mammals drastically lower their rate of oxygen consumption and body temperature (Tb) for up to several weeks, but regularly rewarm and stay euthermic for brief periods (&lt; 30 h). It has been hypothesized that these periodic arousals are driven by the development of a metabolic imbalance during torpor, that is, the accumulation or the depletion of metabolites or the accrual of cellular damage that can be eliminated only in the euthermic state. We obtained oxygen consumption (as a proxy of metabolic rate) and Tb at 7-minute intervals over entire torpor-arousal cycles in the garden dormouse (Eliomys quercinus). Torpor bout duration was highly dependent on mean oxygen consumption during the torpor bout. Oxygen consumption during torpor, in turn, was elevated by Tb, which fluctuated only slightly in dormice kept at∼3-8°C. This corresponds to a well-known effect of higher Tb on shortening torpor bout lengths in hibernators. Arousal duration was independent from prior torpor length, but arousal mean oxygen consumption increased with prior torpor Tb. These results, particularly the effect of torpor oxygen consumption on torpor bout length, point to an hourglass mechanism of torpor control, i.e., the correction of a metabolic imbalance during arousal. This conclusion is in line with previous comparative studies providing evidence for significant interspecific inverse relationships between the duration of torpor bouts and metabolism in torpor. Thus, a simple hourglass mechanism is sufficient to explain torpor/arousal cycles, without the need to involve non-temperature-compensated circadian rhythms.

Neurons in the dorsomedial hypothalamus promote, prolong, and deepen torpor

Torpor is a naturally occurring, hypometabolic, hypothermic state engaged by a wide range of animals in response to imbalance between the supply and demand for nutrients. Recent work has identified some of the key neuronal populations involved in daily torpor induction in mice, in particular projections from the preoptic area of the hypothalamus (POA) to the dorsomedial hypothalamus (DMH). The DMH plays a role in thermoregulation, control of energy expenditure, and circadian rhythms, making it well positioned to contribute to the expression of torpor. We used activity dependent genetic TRAPing techniques to target DMH neurons that were active during natural torpor bouts in female mice. Chemogenetic reactivation of torpor-TRAPed DMH neurons in calorie-restricted mice promoted torpor, resulting in longer and deeper torpor bouts. Chemogenetic inhibition of torpor-TRAPed DMH neurons did not block torpor entry, suggesting a modulatory but not a necessary role for the DMH in the control of torpor. This work adds to the evidence that a projection from the POA to the DMH forms part of a torpor-inducing circuit within the mouse hypothalamus.

Tropical bats counter heat by combining torpor with adaptive hyperthermia

Many tropical mammals are vulnerable to heat because their water budget limits the use of evaporative cooling for heat compensation. Further increasing temperatures and aridity might consequently exceed their thermoregulatory capacities. Here, we describe two novel modes of torpor, a response usually associated with cold or resource bottlenecks, as efficient mechanisms to counter heat. We conducted a field study on the Malagasy bat Macronycteris commersoni resting in foliage during the hot season, unprotected from environmental extremes. On warm days, the bats alternated between remarkably short micro-torpor bouts and normal resting metabolism within a few minutes. On hot days, the bats extended their torpor bouts over the hottest time of the day while tolerating body temperatures up to 42.9°C. Adaptive hyperthermia combined with lowered metabolic heat production from torpor allows higher heat storage from the environment, negates the need for evaporative cooling and thus increases heat tolerance. However, it is a high-risk response as the torpid bats cannot defend body temperature if ambient temperature increases above a critical/lethal threshold. Torpor coupled with hyperthermia and micro-torpor bouts broaden our understanding of the basic principles of thermal physiology and demonstrate how mammals can perform near their upper thermal limits in an increasingly warmer world.

Breeding and hibernation of captive meadow jumping mice (Zapus hudsonius)

Hibernating mammals exhibit unique metabolic and physiological phenotypes that have potential applications in medicine or spaceflight, yet our understanding of the genetic basis and molecular mechanisms of hibernation is limited. The meadow jumping mouse, a small North American hibernator, exhibits traits – including a short generation time – that would facilitate genetic approaches to hibernation research. Here we report the collection, captive breeding, and laboratory hibernation of meadow jumping mice. Captive breeders in our colony produced a statistically significant excess of male offspring and a large number of all-male and all-female litters. We confirmed that short photoperiod induced pre-hibernation fattening, and cold ambient temperature facilitated entry into hibernation. During pre-hibernation fattening, food consumption exhibited non-linear dependence on both body mass and temperature, such that food consumption was greatest in the heaviest animals at the coldest temperatures. Meadow jumping mice exhibited a strong circadian rhythm of nightly activity that was disrupted during the hibernation interval. We quantified the length and timing of torpor bouts and arousals obtained from an uninterrupted recording of a hibernating female. Over a 90.6 day hibernation interval, torpor bouts ranged from 2.1 to 12.8 days (mean 7.7 days), and arousal length was relatively constant with a mean length of 9.6 hours. We conclude that it is possible to study hibernation phenotypes using captive-bred meadow jumping mice in a laboratory setting.

Hibernation in a primate: does sleep occur?

During hibernation, critical physiological processes are downregulated and thermogenically induced arousals are presumably needed periodically to fulfil those physiological demands. Among the processes incompatible with a hypome tabolic state is sleep. However, one hibernating primate, the dwarf lemur Cheirogaleus medius , experiences rapid eye movement (REM)-like states during hibernation, whenever passively reaching temperatures above 30°C, as occurs when it hibernates in poorly insulated tree hollows under tropical conditions. Here, we report electroencephalographic (EEG) recordings, temperature data and metabolic rates from two related species ( C. crossleyi and C. sibreei ), inhabiting high-altitude rainforests and hibernating underground, conditions that mirror, to some extent, those experienced by temperate hibernators. We compared the physiology of hibernation and spontaneous arousals in these animals to C. medius , as well as the much more distantly related non-primate hibernators, such as Arctic, golden-mantled and European ground squirrels. We observed a number of commonalities with non-primate temperate hibernators including: (i) monotonous ultra-low voltage EEG during torpor bouts in these relatively cold-weather hibernators, (ii) the absence of sleep during torpor bouts, (iii) the occurrence of spontaneous arousals out of torpor, during which sleep regularly occurred, (iv) relatively high early EEG non-REM during the arousal, and (v) a gradual transition to the torpid EEG state from non-REM sleep. Unlike C. medius , our study species did not display sleep-like states during torpor bouts, but instead exclusively exhibited them during arousals. During these short euthermic periods, non-REM as well as REM sleep-like stages were observed. Differences observed between these two species and their close relative, C. medius , for which data have been published, presumably reflect differences in hibernaculum temperature.

Late-born intermittently fasted juvenile garden dormice use torpor to grow and fatten prior to hibernation: consequences for ageing processes

Torpor is thought to slow age-related processes and to sustain growth and fattening of young individuals. Energy allocation into these processes represents a challenge for juveniles, especially for those born late in the season. We tested the hypothesis that late-born juvenile garden dormice ( Eliomys quercinus ) fed ad libitum (‘AL’, n = 9) or intermittently fasted (‘IF’, n = 9) use short torpor bouts to enhance growth and fat accumulation to survive winter. IF juveniles displayed more frequent and longer torpor bouts, compared with AL individuals before hibernation. Torpor frequency correlated negatively with energy expenditure and water turnover. Hence, IF juveniles gained mass at the same rate, reached similar pre-hibernation fattening and displayed identical hibernating patterns and mass losses as AL animals. We found no group differences in relative telomere length (RTL), an indicator of ageing, during the period of highest summer mass gain, despite greater torpor use by IF juveniles. Percentage change in RTL was negatively associated with mean and total euthermic durations among all individuals during hibernation. We conclude that torpor use promotes fattening in late-born juvenile dormice prior to hibernation. Furthermore, we provided the first evidence for a functional link between time spent in euthermy and ageing processes over winter.

Refuge sites, activity and torpor in wild common dunnarts (Sminthopsis murina) in a temperate heathland

This telemetric study describes patterns of movement, activity, refuge-site use and torpor in free-living Sminthopsis murina over one autumn/winter period in a warm-temperate habitat. S. murina were found to rest during the day in burrows and hollow logs. Individuals maintained several daytime refuges and foraged over several hectares each night. They were found to prefer agamid burrows where a daily temperature of 10.3–15.8°C was maintained when ambient surface temperatures varied between 3.5 and 24.6°C. Torpor was employed in 12 of 13 complete resting periods recorded. Dunnarts were found to use both long (>6 h) and short (<4 h) torpor bouts with a minimum skin temperature of 17.2–26.7°C. Typically, torpor occurred in the morning, though bouts into the afternoon were also recorded. Arousal rates from torpor were variable and were achieved by endogenous and passive means. Normothermic rest bouts tended to be short (mostly <3 h) though longer periods were recorded, with a mean resting skin temperature of 32.3 ± 0.8°C. The variable physiological responses observed in S. murina seem to follow a facultative pattern, and, along with long activity periods and their use of refuge sites, may be linked to variable invertebrate activity during cooler months.