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Neural and behavioural correlates of consciousness: the welfare consequences of fatal hyperbaric and hypercapnic hypoxia in laboratory mice

Lookup NU author(s): Dr Jasmine ClarksonORCiD, Dr Ross MuersORCiD, Dr Matthew Leach, Dr Jessica MartinORCiD

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

The ability to understand an animal’s capacity to experience negative sensations, such as pain and distress, during impaired states of consciousness is important for a wide variety of situations, and particularly when animals are being killed. Mice remain the predominant species used for scientific research globally, where a prerequisite requires them to be humanely killed at the end of the scientific work. However, the ability of some existing practices and methodologies to provide these animals with a humane death have been questioned (e.g. exposure to a rising concentration of carbon dioxide), thus requiring the development of novel, refined methodologies. We highlight the potential of hypobaric hypoxia to provide a humane alternative to hypercapnic hypoxia by combining behavioural with neurophysiological assessment (using electroencephalography, EEG) to characterise brain activity during the induction of unconsciousness. We demonstrate different patterns of brain activity between hypobaric and hypercapnic hypoxia, suggestive of key mechanistic differences in the transition towards unconsciousness. Unlike hypercapnic hypoxia, hypobaric hypoxia resulted in an early shift in peak power to lower delta frequency bands (<4Hz), suggestive of early cognitive impairment and an anaesthetic-like state before loss of posture. As such, mice are likely to have a reduced capacity to experience negative sensations such as distress and anxiety. Hypobaric hypoxia could provide the basis for major refinement to essential killing practices for laboratory mice worldwide.


Publication metadata

Author(s): Clarkson JM, McKeegan DEF, Muers RS, Leach MC, Sparrey J, Gonzalez-Sulser A, Martin JE

Publication type: Article

Publication status: Published

Journal: Lab Animal

Year: 2026

Issue: ePub ahead of print

Online publication date: 21/08/2026

Acceptance date: 21/07/2026

Date deposited: 22/07/2026

ISSN (print): 0093-7355

ISSN (electronic): 1548-4475

Publisher: Springer

URL: https://doi.org/10.1038/s41684-026-01788-5

DOI: 10.1038/s41684-026-01788-5

ePrints DOI: 10.57711/sv10-z720

Data Access Statement: Data supporting this study are openly available in Zenodo at 10.5281/zenodo.21220901.


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Funding

Funder referenceFunder name
BBSRC - BB/P013759/1
BBSRC - BB/S007210/1

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