Hibernation is essential for survival during seasonal deficiencies in food supply in several species of mammals. Torpor, or severe metabolic suppression, protects the body during the hibernating season by reducing resting metabolic rate and core body temperature. Seasonal hibernators, such as the arctic ground squirrel, follow a circannual cycle and are able to spontaneously enter torpor only during the hibernation season. A two-switch model of transition into the torpid state suggests that one physiological switch signals the onset of the hibernation season, and another switch initiates the onset of torpor.

The mechanism for transition into the torpid state, which includes altered central nervous system (CNS) control of thermoregulation, extended sleep, active inhibition of metabolism and temperature-dependent effects on metabolic rate, has been previously unknown. Now, a team led by Kelly L. Drew (University of Alaska, Fairbanks) has found that a seasonal change in the CNS response to a molecule called adenosine may provide that mechanism (J. Neurosci. 31, 10752–10758; 2011).

Credit: Harry Kolenbrander

Signaling via A1 adenosine receptors (A1ARs), termed purinergic signaling, mediates sleep drive and decreases body temperature. In this study, blockade of the A1AR receptors in the CNS using the antagonist CPT was shown to reverse torpor onset in all animals. This indicates that activation of A1AR is necessary for the onset of spontaneous torpor in the arctic ground squirrel.

Additionally, the A1AR agonist CHA induced a torpor-like effect in the animals that increased as the hibernation season progressed. These results indicate that A1AR activation within the CNS is necessary and sufficient to induce torpor during the hibernation season but not during the off-season when arctic ground squirrels do not spontaneously hibernate.

The results of this study show that the CNS regulates the onset of torpor via the activation of A1AR. In the context of the two-switch model, the seasonally increased sensitivity to central purinergic signaling serves as the first switch to signal the onset of hibernation; stimulation of central A1AR by endogenous adenosine serves as a second switch that induces torpor. The authors hypothesize that the mechanism underlying the first switch may involve changes in purinergic receptor expression or function; in extracellular levels of adenosine; or in neural circuits regulating sleep, metabolism or body temperature.

Understanding how hibernating mammals regulate metabolic suppression has potential to translate to improved therapies for conditions in which oxygen and energy supply fail to meet demand, including stroke, cardiac arrest, hemorrhagic shock and trauma.