Neural and behavioral correlates of consciousness: the welfare consequences of fatal hypobaric and hypercapnic hypoxia in laboratory mice

Understanding an animal's capacity to experience negative sensations, such as pain and distress, during impaired states of consciousness is critical in many contexts, particularly when animals are being euthanized. 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, whether some of the existing practices and methodologies (for example, exposure to a rising concentration of carbon dioxide) provide these animals with a humane death has been questioned, thus requiring the development of novel, refined methodologies. Here we highlight the potential of hypobaric hypoxia to provide a humane alternative to hypercapnic hypoxia by combining behavioral and neurophysiological assessment (using electroencephalography) to characterize brain activity during the induction of unconsciousness. We found different patterns of brain activity between hypobaric and hypercapnic hypoxia, suggestive of key mechanistic differences in the transition toward unconsciousness. Unlike hypercapnic hypoxia, hypobaric hypoxia resulted in an early shift in peak power to lower delta frequency bands (<4 Hz), suggestive of early cognitive impairment and an anesthetic-like state before loss of posture. As such, mice are likely to have a reduced capacity to have negatively valenced sensory-affective experiences. Hypobaric hypoxia could provide the basis for major refinement to essential killing practices for laboratory mice worldwide.