Molecular and Metabolic Aspects of Mammalian Hibernation - Expression of the hibernation phenotype results from the coordinated regulation of multiple physiological and molecular events during preparation for and entry into torpor

713 eat seeds from cones and are too large to use the subnivian space; for these animals, winter can be a long season without foraging opportunities, and they have therefore evolved the ability to pass winter by while in a torpid state of lethargy. A highly regulated sequence of physiological events beginning months in advance of winter coordinates entrance into the suspended state of animation known as hibernation. However, with the exception of bears, which become only moderately hypothermic, no hibernating mammal remains deeply hypothermic for longer than several weeks. Instead, for reasons that are not yet known, they expend significant amounts of energy to periodically rewarm back to normal body temperatures for less than a day before recooling. The seasonal changes in body temperature that occur in an arctic ground squirrel (Spermophilus parryii) living near the edge of its northernmost distribution in Alaska are especially profound and provide an extreme example of hibernation physiology (Figure 1). In a male arctic ground squirrel monitored for body temperature throughout hibernation, minimum body temperature decreased in autumn in parallel with the drop in soil temperature, indicating that when ambient temperatures are above freezing there is a passive thermal equilibrium between arctic ground squirrels and their surroundings. In early December, soil temperatures decreased toward –15 °C, but the ground squirrel’s body temperature remained a constant –2.0 °C during torpor, indicating that this species actively thermoregulates. Substantial thermogenesis is also required throughout hibernation to fuel arousal episodes that interrupt torpor every 10–21 days. Although there is a rich literature of physiological research related to the seasonally programmed changes that prepare the body for hibernation and regulate entry into, maintenance of, and recovery from torpor (e.g., Lyman et al. 1982, Carey et al. 1993, Geiser et al. 1996), the molecular and cellular mechanisms of mammalian hibernation have remained largely a mystery. In this article, against a background of the natural history of hibernation, we focus on recent progress defining the molecular and cellular changes that potentially regulate preparation for and entrance into hibernation and that result in differential regulation of gene products during torpor (FigMolecular and Metabolic Aspects of Mammalian Hibernation