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 (VPGABA) and VP glutamatergic (VPglu) neurons, without affecting cholinergic neurons. VPGABA and VPglu neuronal activity decreased during sevoflurane anaesthesia induction and increased during emergence. Manipulation of VPGABA neurons bidirectionally influenced the duration of induction and emergence. Inhibiting VPglu neurons accelerated induction. Real time activation of VPGABA 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 VPGABA and VPglu neurons in modulating transitions between anaesthesia stages, providing valuable insights into the neuronal mechanisms underlying sevoflurane-induced anaesthesia.
Keywords: GABAergic neurons; general anaesthesia; glutamatergic neurons; sevoflurane; ventral pallidum.
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