Does the Road Traveled Matter? Natural Versus Prematurely Induced Arousal from Torpor

  • Jenifer C. Utz
  • Frank van Breukelen


Although hibernating animals spontaneously arouse from torpor at regular intervals, the practice of prematurely inducing arousal is common. Herein we review the many differences between natural and prematurely induced arousal to address the question of whether these two paths to euthermy are truly synonymous events. We present data demonstrating that the duration of the interbout arousal (IBA) is significantly reduced following a prematurely induced arousal and that the time required to respond to the induction stimulus is influenced by the duration of time spent in torpor. There are numerous alterations in intracellular and whole animal physiology when arousal is prematurely induced; thus we recommend that careful consideration be given to experiments utilizing this type of arousal mechanism.


Brown Adipose Tissue Ground Squirrel Internal Ribosome Entry Site Torpor Bout Arctic Ground Squirrel 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



This work was supported by NSF grant IOB 0448396, awarded to Frank van Breukelen. Jenifer C. Utz was supported by an NSF Graduate Research Fellowship. We thank other members of the laboratory for their diligent efforts.


  1. Barnes BM (1989) Freeze avoidance in a mammal: body temperatures below 0 degree C in an Arctic hibernator. Science 244:1593–1595PubMedCrossRefGoogle Scholar
  2. Baumber J, Denyes A (1965) Oxidation of glucose-U-C14 and palmitate-1-C14 by liver, kidney, and diaphragm from hamsters in cold exposure and hibernation. Can J Biochem 43:747–753PubMedCrossRefGoogle Scholar
  3. Bullard RW, Funkhouser GE (1962) Estimated regional blood flow by rubidium 86 distribution during arousal from hibernation. Am J Physiol 203:266–270PubMedGoogle Scholar
  4. Cannon B, Nedergaard J (2004) Brown adipose tissue: function and physiological significance. Physiol Rev 84:277–359PubMedCrossRefGoogle Scholar
  5. Carey HV, Frank CL, Seifert JP (2000) Hibernation induces oxidative stress and activation of NF-kappa B in ground squirrel intestine. J Comp Physiol B 170:551–559PubMedCrossRefGoogle Scholar
  6. Carey HV, Andrews MT, Martin SL (2003) Mammalian hibernation: cellular and molecular responses to depressed metabolism and low temperature. Physiol Rev 83:1153–1181PubMedGoogle Scholar
  7. Castex C, Tahri A, Hoo-Paris R, Sutter BC (1987) Glucose oxidation by adipose tissue of the edible dormouse (Glis glis) during hibernation and arousal: effect of insulin. Comp Biochem Physiol A 88:33–36PubMedCrossRefGoogle Scholar
  8. Chappell SA, Owens GC, Mauro VP (2001) A 5′ leader of Rbm3, a cold stress-induced mRNA, mediates internal initiation of translation with increased efficiency under conditions of mild hypothermia. J Biol Chem 276:36917–36922PubMedCrossRefGoogle Scholar
  9. Chatfield PO, Lyman CP (1950) Circulatory changes during process of arousal in the hibernating hamster. Am J Physiol 163:566–574PubMedGoogle Scholar
  10. Conte C, Riant E, Toutain C, Pujol F, Arnal JF, Lenfant F, Prats AC (2008) FGF2 translationally induced by hypoxia is involved in negative and positive feedback loops with HIF-1alpha. PLoS ONE 3:e3078PubMedCrossRefGoogle Scholar
  11. Cooper CE, Withers PC (2004) Patterns of body temperature variation and torpor in the numbat, Myrmecobius fasciatus (Marsupialia: Myrmecobiidae). J Thermal Bio 29:277–284CrossRefGoogle Scholar
  12. Cranford JA (1983) Body temperature, heart rate and oxygen consumption of normothermic and heterothermic western jumping mice (Zapus princeps). Comp Biochem Physiol A 74:595–599PubMedCrossRefGoogle Scholar
  13. Cuddihee RW, Fonda ML (1982) Concentrations of lactate and pyruvate and temperature effects on lactate dehydrogenase activity in the tissues of the big brown bat (Eptesicus fuscus) during arousal from hibernation. Comp Biochem Physiol B 73:1001–1009PubMedCrossRefGoogle Scholar
  14. Derij LV, Shtark MB (1985) Hibernators’ brain: protein synthesis in the neocortex and the hippocampus. Comp Biochem Physiol B 80:927–934PubMedCrossRefGoogle Scholar
  15. Eagles DA, Jacques LB, Taboada J, Wagner CW, Diakun TA (1988) Cardiac arrhythmias during arousal from hibernation in three species of rodents. Am J Physiol 254:R102–R108PubMedGoogle Scholar
  16. Fons R, Sender S, Peters T, Jurgens KD (1997) Rates of rewarming, heart and respiratory rates and their significance for oxygen transport during arousal from torpor in the smallest mammal, the Etruscan shrew Suncus etruscus. J Exp Biol 200:1451–1458PubMedGoogle Scholar
  17. French AR (1982) Effects of temperature on the duration of arousal episodes during hibernation. J Appl Physiol 52:216–220PubMedGoogle Scholar
  18. Genin F, Nibbelink M, Galand M, Perret M, Ambid L (2003) Brown fat and nonshivering thermogenesis in the gray mouse lemur (Microcebus murinus). Am J Physiol Regul Integr Comp Physiol 284:R811–R818PubMedGoogle Scholar
  19. Glass JD, Wang LC (1979) Effects of central injection of biogenic amines during arousal from hibernation. Am J Physiol 236:R162–R167PubMedGoogle Scholar
  20. Hermes ML, Kalsbeek A, Kirsch R, Buijs RM, Pevet P (1993) Induction of arousal in hibernating European hamsters (Cricetus cricetus L.) by vasopressin infusion in the lateral septum. Brain Res 631:313–316PubMedCrossRefGoogle Scholar
  21. Hintz DR, Hall KD (1988) The influence of ambient temperature on rate of arousal and behavioral changes during arousal from hibernation in the 13-lined ground squirrel, Spermophilus tridecimlineatus. Bios 57:109–120Google Scholar
  22. Holcik M, Sonenberg N, Korneluk RG (2000) Internal ribosome initiation of translation and the control of cell death. Trends Genet 16:469–473PubMedCrossRefGoogle Scholar
  23. Holcik M, Sonenberg N (2005) Translational control in stress and apoptosis. Nature Rev Mol Cell Biol 6:318–327CrossRefGoogle Scholar
  24. Horwitz BA, Smith RE, Pengelley ET (1968) Estimated heat contribution of brown fat in arousing ground squirrels (Citellus lateralis). Am J Physiol 214:115–121PubMedGoogle Scholar
  25. Karpovich SA, Tøien Ø, Buck CL, Barnes BM (2009) Energetics of arousal episodes in hibernating arctic ground squirrels. J Comp Physiol B 179:691–700PubMedCrossRefGoogle Scholar
  26. Kauffman AS, Paul MJ, Zucker I (2004) Increased heat loss affects hibernation in golden-mantled ground squirrels. Am J Physiol Regul Integr Comp Physiol 287:R167–R173PubMedCrossRefGoogle Scholar
  27. Klain GJ, Whitten BK (1968a) Carbon dioxide fixation during hibernation and arousal from hibernation. Comp Biochem Physiol 25:363–366PubMedCrossRefGoogle Scholar
  28. Klain GJ, Whitten BK (1968b) Plasma free amino acids in hibernation and arousal. Comp Biochem Physiol 27:617–619PubMedCrossRefGoogle Scholar
  29. Kruman II, Ilyasova EN, Rudchenko SA, Khurkhulu ZS (1988) The intestinal epithelial cells of ground squirrel (Citellus undulatus) accumulate at G2 phase of the cell cycle throughout a bout of hibernation. Comp Biochem Physiol A Physiol 90:233–236CrossRefGoogle Scholar
  30. Lang KJ, Kappel A, Goodall GJ (2002) Hypoxia-inducible factor-1 alpha mRNA contains an internal ribosome entry site that allows efficiency translation during normoxia and hypoxia. Mol Biol Cell 13:1792–1801PubMedCrossRefGoogle Scholar
  31. Lee M, Choi I, Park K (2002) Activation of stress signaling molecules in bat brain during arousal from hibernation. J Neurochem 82:867–873PubMedCrossRefGoogle Scholar
  32. Ma YL, Wu SF (2008) Simultaneous measurement of brain tissue oxygen partial pressure, temperature, and global oxygen consumption during hibernation, arousal, and euthermy in non-sedated and non-anesthetized Arctic ground squirrels. J Neurosci Methods 174:237–244PubMedCrossRefGoogle Scholar
  33. Malan A, Mioskowski E, Calgari C (1988) Time-course of blood acid-base state during arousal from hibernation in the European hamster. J Comp Physiol B 158:495–500PubMedCrossRefGoogle Scholar
  34. Martin SL, Maniero GD, Carey C, Hand SC (1999) Reversible depression of oxygen consumption in isolated liver mitochondria during hibernation. Physiol Biochem Zool 72:255–264PubMedCrossRefGoogle Scholar
  35. Merrick WC (2004) Cap-dependent and cap-independent translation in eukaryotic systems. Gene 332:1–11PubMedCrossRefGoogle Scholar
  36. Milsom WK, Zimmer MB, Harris MB (1999) Regulation of cardiac rhythm in hibernating mammals. Comp Biochem Physiol A Mol Integr Physiol 124:383–391PubMedCrossRefGoogle Scholar
  37. Milsom WK, Zimmer MB, Harris MB (2001) Vagal control of cardiorespiratory function in hibernation. Exp Physiol 86:791–796PubMedCrossRefGoogle Scholar
  38. Mrosovsky N, Fisher KC (1970) Sliding set points for body weight in ground squirrels during the hibernation season. Can J Zool 48:241–247PubMedCrossRefGoogle Scholar
  39. Muchlinski AE, Carlisle AL (1982) Urine concentration by an undisturbed, naturally arousing hibernator (Spermophilus lateralis): water-balance implications. J Mammal 63:510–512CrossRefGoogle Scholar
  40. Musaccahia XJ, Hamilton RD (1959) Notes on hibernation and awakening in Arctic ground squirrels. J Mammal 40:201–204CrossRefGoogle Scholar
  41. Nicol SC, Andersen NA (2008) Rewarming rates and thermogenesis in hibernating echidnas. Comp Biochem Physiol A Mol Integr Physiol 150:189–195PubMedCrossRefGoogle Scholar
  42. Opazo JC, Nespolo RF, Bozinovic F (1999) Arousal from torpor in the Chilean mouse-opposum (Thylamys elegans): does non-shivering thermogenesis play a role? Comp Biochem Physiol A Mol Integr Physiol 123:393–397PubMedCrossRefGoogle Scholar
  43. Orr AL, Lohse LA, Drew KL, Hermes-Lima M (2009) Physiological oxidative stress after arousal from hibernation in Arctic ground squirrel. Comp Biochem Physiol A Mol Integr Physiol 153:213–221PubMedCrossRefGoogle Scholar
  44. Osborne PG, Hashimoto M (2003) State-dependent regulation of cortical blood flow and respiration in hamsters: response to hypercapnia during arousal from hibernation. J Physiol 547:963–970PubMedCrossRefGoogle Scholar
  45. Osborne PG, Sato J, Shuke N, Hashimoto M (2005) Sympathetic alpha-adrenergic regulation of blood flow and volume in hamsters arousing from hibernation. Am J Physiol Regul Integr Comp Physiol 289:R554–R562PubMedCrossRefGoogle Scholar
  46. Pan P, van Breukelen F (2011) Preference of IRES-mediated initiation of translation during hibernation in golden-mantled ground squirrels, Spermophilus lateralis. Am J Physiol Regul Integr Comp Physiol 301:R370–R377PubMedCrossRefGoogle Scholar
  47. Pengelley ET, Fisher KC (1968) Ability of ground squirrel Citellus lateralis to be habituated to stimuli while in hibernation. J Mammal 49:561–562PubMedCrossRefGoogle Scholar
  48. Phillips PK, Heath JE (2004) Comparison of surface temperature in 13-lined ground squirrel (Spermophilus tridecimlineatus) and yellow-bellied marmot (Marmota flaviventris) during arousal from hibernation. Comp Biochem Physiol A Mol Integr Physiol 138:451–457PubMedCrossRefGoogle Scholar
  49. Popovic VP, Kent BB (1969) Alteration of activity rhythm after induced arousal from hibernation. Rassegna di neurologia vegetativa 23:27–36PubMedGoogle Scholar
  50. Rauch JC, Hayward JS (1970) Regional distribution of blood flow in the bat (Myotis lucifugus) during arousal from hibernation. Can J Physiol Pharm 48:269–273CrossRefGoogle Scholar
  51. Rauch JC, Beatty DD (1975) Comparison of regional blood distribution in Eptesicus fuscus (big brown bat) during torpor (summer), hibernation (winter), and arousal. Can J Zool 53:207–214PubMedCrossRefGoogle Scholar
  52. Robertson WD, Yousef MK, Johnson HD (1968) Simultaneous recording of core temperature and energy expenditure during the hibernation cycle of Mesocricetus auratus. Nature 219:742–743PubMedCrossRefGoogle Scholar
  53. Steffen JM, Riedesel ML (1982) Pulmonary ventilation and cardiac activity in hibernating and arousing golden-mantled ground squirrels (Spermophilus lateralis). Cryobiology 19:83–91PubMedCrossRefGoogle Scholar
  54. Stone GN, Purvis A (1992) Warm-up rates during arousal from torpor in heterothermic mammals: physiological correlates and a comparison with heterothermic insects. J Comp Physiol B 162:284–295PubMedCrossRefGoogle Scholar
  55. Tähti H, Soivio A (1977) Respiratory and circulatory differences between induced and spontaneous arousals in hibernating hedgehogs (Erinaceus europaeus L). Ann Zool Fenn 14:198–203Google Scholar
  56. Tähti H, Soivio A (1978) Comparison of induced and spontaneous arousals in hibernating hedgehogs. Experientia Suppl 22:321–325Google Scholar
  57. Tøien Ø, Drew KL, Chao ML, Rice ME (2001) Ascorbate dynamics and oxygen consumption during arousal from hibernation in Arctic ground squirrels. Am J Physiol Regul Integr Comp Physiol 281:R572–R583PubMedGoogle Scholar
  58. Twente JW, Twente JA (1965a) Effects of core temperature upon duration of hibernation of Citellus lateralis. J Appl Physiol 20:411–416PubMedGoogle Scholar
  59. Twente JW, Twente JA (1965b) Regulation of hibernating periods by temperature. PNAS 54:1058–1061PubMedCrossRefGoogle Scholar
  60. Twente JW, Twente JA (1968) Progressive irritability of hibernating Citellus lateralis. Comp Biochem Physiol 25:467–474PubMedCrossRefGoogle Scholar
  61. Twente JW, Twente J, Moy RM (1977) Regulation of arousal from hibernation by temperature in three species of Citellus. J Appl Physiol 42:191–195PubMedGoogle Scholar
  62. Utz JC, Velickovska V, Shmereva A, van Breukelen F (2007) Temporal and temperature effects on the maximum rate of rewarming from hibernation. J Thermal Bio 32:276–281CrossRefGoogle Scholar
  63. van Breukelen F, Martin SL (2001) Translational initiation is uncoupled from elongation at 18 degrees C during mammalian hibernation. Am J Physiol Regul Integr Comp Physiol 281:R1374–R1379PubMedGoogle Scholar
  64. van Breukelen F, Carey HV (2002) Ubiquitin conjugate dynamics in the gut and liver of hibernating ground squirrels. J Comp Physiol B 172:269–273PubMedCrossRefGoogle Scholar
  65. van Breukelen F, Martin SL (2002a) Invited review: molecular adaptations in mammalian hibernators: unique adaptations or generalized responses? J Appl Physiol 92:2640–2647PubMedGoogle Scholar
  66. van Breukelen F, Martin SL (2002b) Reversible depression of transcription during hibernation. J Comp Physiol B 172:355–361PubMedCrossRefGoogle Scholar
  67. van Breukelen F, Sonenberg N, Martin SL (2004) Seasonal and state-dependent changes of eIF4E and 4E-BP1 during mammalian hibernation: implications for the control of translation during torpor. Am J Physiol Regul Integr Comp Physiol 287:R349–R353PubMedCrossRefGoogle Scholar
  68. Velickovska V, Lloyd BP, Qureshi S, van Breukelen F (2005) Proteolysis is depressed during torpor in hibernators at the level of the 20S core protease. J Comp Physiol B 175:329–335PubMedCrossRefGoogle Scholar
  69. Velickovska V, van Breukelen F (2007) Ubiquitylation of proteins in livers of hibernating golden-mantled ground squirrels, Spermophilus lateralis. Cryobiol 55:230–235CrossRefGoogle Scholar
  70. Wells LA (1971) Circulatory patterns of hibernators. Am J Physiol 221:1517–1520PubMedGoogle Scholar
  71. Weltzin MM, Zhao HW, Drew KL, Bucci DJ (2006) Arousal from hibernation alters contextual learning and memory. Behav Brain Res 167:128–133PubMedCrossRefGoogle Scholar
  72. Whitten BK, Burlington RF, Posiviata MA (1974) Temporal changes in amino acid catabolism during arousal from hibernation in the golden-mantled ground squirrel. Comp Biochem Physiol A 47:541–546PubMedCrossRefGoogle Scholar
  73. Withers PC (1992) Comparative animal physiology. Saunders College Publishing, Fort WorthGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  1. 1.School of Life SciencesUniversity of NevadaLas VegasUSA

Personalised recommendations