# Subtype-specific modulation of inhibitory interneurons by general anesthetics

## TL;DR

This study shows how different anesthetics affect brain cells, with ketamine uniquely activating certain neurons unlike other anesthetics.

## Contribution

The study reveals ketamine's unique activation of excitatory and SST interneurons compared to isoflurane and propofol.

## Key findings

- All anesthetics suppress excitatory and inhibitory neuronal activity in the cortex.
- Ketamine preferentially activates SST interneurons compared to isoflurane and propofol.
- Ketamine induces a distinct cortical reconfiguration compared to GABAergic anesthetics.

## Abstract

The mechanisms by which general anesthetics induce loss of consciousness remain unclear, particularly regarding their cell-type-specific effects on cortical circuits. Using in vivo 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.

•General anesthetics broadly suppress excitatory and inhibitory neuronal activity in the cortex•Ketamine uniquely activates subsets of excitatory neurons despite overall suppression•SST interneurons are preferentially activated by ketamine, unlike PV interneurons•Ketamine induces a distinct cortical reconfiguration compared with GABAergic anesthetics

General anesthetics broadly suppress excitatory and inhibitory neuronal activity in the cortex

Ketamine uniquely activates subsets of excitatory neurons despite overall suppression

SST interneurons are preferentially activated by ketamine, unlike PV interneurons

Ketamine induces a distinct cortical reconfiguration compared with GABAergic anesthetics

Natural sciences; Biological sciences; Neuroscience; Molecular neuroscience; Cellular neuroscience