Ventral pallidum GABAergic and glutamatergic neurons modulate arousal during sevoflurane general anaesthesia in male mice

Abstract Background and Purpose The induction and emergence of general anaesthesia involve an altered process of states of consciousness, yet the central nervous system mechanisms remain inadequately understood. The ventral pallidum (VP) within the basal ganglia is crucial in sleep–wake modulation. However, its involvement in general anaesthesia and the underlying neuronal mechanisms are not well elucidated. Experimental Approach In vivo electrophysiological recordings were conducted to examine changes in the activity of different types of VP neurons before and after sevoflurane exposure. Fibre photometry, combined with electroencephalogram and electromyography recordings, was employed to analyse neuronal activity during both the induction and recovery phases of sevoflurane anaesthesia. Chemogenetics was implemented to investigate the impact of modulated neuronal activity on anaesthesia induction and emergence, whereas optogenetics was used for real time activation of neurons at different depths of anaesthesia. Key Results Sevoflurane exposure reduced the firing activity of both VP GABAergic (VP GABA ) and VP glutamatergic (VP glu ) neurons, without affecting cholinergic neurons. VP GABA and VP glu neuronal activity decreased during sevoflurane anaesthesia induction and increased during emergence. Manipulation of VP GABA neurons bidirectionally influenced the duration of induction and emergence. Inhibiting VP glu neurons accelerated induction. Real time activation of VP GABA neurons triggered cortical activation and behavioural emergence during steady‐state sevoflurane anaesthesia and reduced the burst suppression ratio during deep anaesthesia. Conclusion and Implications These findings highlight the role of VP GABA and VP glu neurons in modulating transitions between anaesthesia stages, providing valuable insights into the neuronal mechanisms underlying sevoflurane‐induced anaesthesia.