Psychedelic compounds directly excite 5-HT2A layer V medial prefrontal cortex neurons through 5-HT2A Gq activation
Translational Psychiatry October 6, 2025 Gavin P. Schmitz, Yi-Ting Chiu, Mia L. Foglesong et al. 13 citations
Psilocybin's active metabolite psilocin increases activity in the medial prefrontal cortex (mPFC), a brain region rich in 5-HT2A receptors. A specific population of neurons in the prelimbic/anterior cingulate mPFC that express these receptors becomes more excitable and fires more in response to psilocin and a selective 5-HT2A receptor compound, effects dependent on both the receptor and Gα q signaling. A novel non-hallucinogenic psychedelic compound produced similar effects. These results point to membrane-bound 5-HT2A receptors and intracellular Gα q signaling as potential therapeutic targets for psychedelic-associated plasticity.