Science, Medicine, and the Anesthesiologist

Microglia, the resident immune cells of the central nervous system, regulate and remodel neuronal activity by contacting pre- and postsynaptic elements and executing synaptic pruning and promoting spine formation. However, the role of microglia in the context of anesthesia, specifically during cessation of general anesthesia, is unknown. Using in vivo two-photon imaging combined with electron microscopy (including nanoscale serial block-face scanning electron microscopy with 3-dimentional reconstruction) in virally transfected and genetically modified mice, the role of microglia on neuronal activity in the somatosensory cortex was investigated during and after general anesthesia with isoflurane. During emergence from anesthesia, there was a period of microglia-mediated hyperactivity accompanied by increased sensory perception with lower pain reflex threshold, which gradually returned to initial awake baseline levels. Additional experiments revealed that new microglial bulbous endings formed during anesthesia within 30 min, which shielded inhibitory γ-aminobutyric acid–mediated synapses from interacting with neurons of the somatosensory cortex through physical barrier formation into the synaptic cleft, resulting in temporarily increased neuronal hyperactivity during emergence from anesthesia over a period of 60 min. Mechanistic studies further showed that selective conditional deletion of the highly expressed β2-adrenergic receptor in microglia, similar to microglial ablation, prevented postanesthesia neuronal hyperactivity.