Somatostatin-expressing Neurons in the Medial Prefrontal Cortex Promote Sevoflurane Anesthesia in Mice.

Summary

In mice, medial prefrontal somatostatin interneurons (SST-INs) are activated during sevoflurane anesthesia. Chemogenetic manipulation of SST-INs bidirectionally altered recovery time, and SST activation increased time-locked GABA input while suppressing pyramidal calcium signals. Increased GABA input preceded loss of righting, indicating a causal cortical microcircuit mechanism enhancing anesthetic effect.

Key Findings

• SST-IN c-Fos expression increased during sevoflurane (26.4% vs 48.0%; P=0.0007).
• Chemogenetic inhibition/activation of SST-INs shortened (84→51 s; P=0.008) or prolonged (97→140 s; P=0.006) recovery from sevoflurane.
• GABA input to pyramidal neurons rose before loss of righting (0.46%→2.25%; P=0.031), and SST activation reduced pyramidal Ca signals (−0.14%→−10.08%; P=0.002).

Clinical Implications

While preclinical, these data support cortical microcircuit contributions to anesthetic depth, potentially guiding EEG biomarkers and strategies for individualized anesthesia or emergence modulation.

Limitations

• Mouse model limits direct clinical generalizability
• Focused on sevoflurane; cross-anesthetic generalization remains to be established

Future Directions

Map upstream/downstream SST-IN circuits, test other anesthetics, and translate to human biomarkers (EEG features) for cortical inhibitory tone during anesthesia.