Psychedelic compounds directly excite 5-HT_2A layer V medial prefrontal cortex neurons through 5-HT_2A Gq activation.

ABSTRACT: Psilocybin, and its active metabolite psilocin, have seen renewed interest due to studies suggesting potential therapeutic utility. 5-Hydroxytryptamine2A receptors (5-HT_2ARs) are primary mediators of the psychoactive effects of psychedelics in animals and humans, but the underlying neurobiological mechanisms remain poorly understood. Functional magnetic resonance imaging identified significant psilocin-induced increases in medial prefrontal cortex (mPFC) activity, a site of enriched 5-HT_2AR expression. We identified a population of 5-HT_2AR neurons in the prelimbic/anterior cingulate mPFC. Psilocin and the 5-HT_2AR-selective compound 25-CN-NBOH increased excitability, and stimulated firing across a range of current injections in these neurons that

SUBMITTER: Schmitz GP 

PROVIDER: S-EPMC12501219 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature