Authors: Luo L, et al.
Anesthesiology ():10.1097/ALN.0000000000005735, August 28, 2025. doi:10.1097/ALN.0000000000005735
This mouse study investigated whether the parafacial zone (PZ), a GABAergic sleep-promoting region, serves as a common neural node responsible for anesthetic-induced unconsciousness and respiratory depression. By combining chemogenetic and optogenetic approaches, the authors selectively modulated PZ GABAergic neurons and evaluated anesthetic sensitivity, cortical activity, and breathing patterns.
Activation of PZ GABAergic neurons increased sevoflurane potency, shortened induction, delayed emergence, and enhanced cortical suppression. Respiratory rate dropped markedly, showing simultaneous control of arousal and breathing. Optogenetic stimulation during anesthesia intensified burst suppression and reduced respiratory rate. Conversely, inhibition of these neurons decreased anesthetic potency. Interestingly, activating these neurons in awake mice induced a low-arousal state with analgesia and slowed breathing, but without full loss of consciousness.
What You Should Know:
The parafacial zone is a shared neural hub where anesthetic effects on unconsciousness and breathing converge. Its activation helps explain why general anesthetics often depress respiration. Understanding this pathway could guide future efforts to design anesthetic regimens or adjunct therapies that maintain unconsciousness while reducing respiratory risks.
Clinical Relevance:
For anesthesiologists, these findings highlight the importance of monitoring and managing respiratory function during anesthesia. While this work is preclinical, it underscores the need for vigilance with volatile anesthetics, particularly in vulnerable populations. It also points toward potential targets for developing drugs that separate sedative effects from respiratory depression.
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