Psilocybin reshapes cortical inhibition through selective interneuron recruitment.

Psilocybin reduces the firing of somatostatin-expressing interneurons while increasing the activity of parvalbumin-expressing interneurons in the mouse medial frontal cortex.

• GABAergic neurons, including somatostatin and parvalbumin-expressing interneurons, respond differently to psilocybin.
• The decrease in activity of somatostatin-expressing interneurons is linked to the 5-HT1A receptor.
• In contrast, the activity of parvalbumin-expressing interneurons increases with psilocybin treatment.
• The effects observed are specific to certain types of GABAergic interneurons and do not involve vasoactive intestinal peptide-expressing interneurons.
• These findings suggest that psilocybin alters cortical inhibition in a targeted manner.

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