Subtype-specific modulation of inhibitory interneurons by general anesthetics

The mechanisms by which general anesthetics induce loss of consciousness remain unclear, particularly regarding their cell-type-specific effects on cortical circuits. Using <i>in vivo</i> two-photon calcium imaging, we compared the effects of isoflurane, propofol, and ketamine-administered at equivalent sedative depth based on behavioral reflex suppression-on excitatory neurons and inhibitory interneuron subtypes (PV and SST) in the mouse somatosensory cortex. All anesthetics suppressed excitatory and inhibitory neuronal activity at the population level. However, ketamine uniquely increased the activity of a larger fraction of excitatory neurons (17.6 ± 3.1%) than isoflurane (4.0 ± 1.9%) or propofol (4.1 ± 2.1%). Similar effects were observed in inhibitory neurons. While PV interneurons showed no anesthetic-specific differences, SST interneurons were preferentially activated by ketamine (25.9 ± 6.0%) compared with isoflurane and propofol. These findings indicate that ketamine selectively enhances activity in subsets of excitatory and SST interneurons, revealing a distinct cortical reconfiguration underlying anesthetic action.