The physiological signature of daily torpor is not orexin dependent

Abstract

Under conditions of scarce food availability and cool ambient temperature, the mouse (Mus Musculus) enters into torpor, a state of transient metabolic suppression mediated in part by the autonomic nervous system. Hypothalamic orexins are involved in the coordination of behaviors and autonomic function. We tested whether orexins are necessary for the coordinated changes in physiological variables, which underlie torpor and represent its physiological signature. We performed simultaneous measurements of brain temperature, electroencephalographic, and electromyographic activity allowing objective assessment of wake–sleep behavior, and cardiovascular, respiratory, and metabolic variables in orexin knockout mice (ORX-KO) and wild-type mice (WT) during torpor bouts elicited by caloric restriction and mild cold stress. We found that torpor bouts in WT are characterized by an exquisitely coordinated physiological signature. The characteristics of torpor bouts in terms of duration and rate of change of brain temperature and electromyographic activity at torpor entrance and exit did not differ significantly between ORX-KO and WT, and neither did the cardiovascular, respiratory, and metabolic characteristics of torpor. ORX-KO and WT also had similar wake–sleep state changes associated with torpor bouts, with the exception of a significantly higher rapid-eye movement sleep time in ORX-KO at torpor entrance. Our results demonstrate that orexins are not necessary either for the normal physiological adaptations occurring during torpor in mice or for their coordination, suggesting that mechanisms different from orexin peptide signaling may be involved in the regulation and the coordination of these physiological responses.

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Acknowledgements

The authors wish to thank Prof. Gerard Heldmaier for generously providing the CaloBox system and its analysis software.

Funding

This research was supported by the University of Bologna (Grants for Fundamental Oriented Research, RFO2017/18, attributed to CB, AS, and GZ) and the European Space Agency (Research agreement collaboration 4000123556  attributed to MC).

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Conception or design of the work: AS, SJS, and GZ. Methodology: VLM, SB, SA, CB, and AV. Formal analysis and investigation: VLM, CB, MC, RA, AS, SJS, and GZ. Writing—original draft preparation: VLM. Writing—original figures preparation: VLM, CB, AS and SJS. Writing—review and editing: all the authors. Funding acquisition: CB, MC, AS, MC and GZ. Supervision: GZ. All authors approved the final version of the manuscript and agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

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Correspondence to Giovanna Zoccoli.

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All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the EU Directive 2010/63/EU for animal experiments and were approved by the Committee on the Ethics of Animal Experiments of the University of Bologna (prot. n. 30209) and of the Italian Ministry of Health (prot. n. 141/2018-PR).

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Lo Martire, V., Berteotti, C., Bastianini, S. et al. The physiological signature of daily torpor is not orexin dependent. J Comp Physiol B 190, 493–507 (2020). https://doi.org/10.1007/s00360-020-01281-6

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Keywords

  • Torpor
  • Orexins/hypocretins
  • Sleep
  • Cardiovascular
  • Ventilation
  • Metabolic rate