Ventrolateral periaqueductal gray GABAergic neurons promote arousal of sevoflurane anesthesia through cortico-midbrain circuit

The mechanism of general anesthesia remains elusive. ventrolateral periaqueductal gray (vlPAG) in the midbrain regulates sleep and awake states. However, role vlPAG its circuits is unclear. We utilized opto/chemogenetics, righting reflex, electroencephalographic recording to assess consciousness changes. employed fiber photometry measure activity neurons neurotransmitters. As a result, showed that GABA decreased during sevoflurane was reactivated after anesthesia. Activating GABAergic promoted arousal anesthesia, while inhibiting them delayed this process. Furthermore, medial prefrontal cortex (mPFC) pyramidal projections ventral tegmental area (VTA) played prominent anesthesia-awake transition. neurotransmitter VTA synchronized with mPFC-vlPAG neuron projections. Therefore, cortico-midbrain centered on exert an arousal-promoting effect