Evi Kostenis

2 papers in the library · 28 citations · publishing 2022-2025

Papers

Psychedelic compounds directly excite 5-HT 2A Layer 5 Pyramidal Neurons in the Prefrontal Cortex through a 5-HT 2A Gq -mediated activation mechanism

bioRxiv (Cold Spring Harbor Laboratory) November 15, 2022 Gavin P. Schmitz, Yi-Ting Chiu, Gabriele M. König et al. 15 citations preprint

Psilocin, the active compound in psilocybin mushrooms, activates serotonin 2A receptors (5-HT2ARs) in the prefrontal cortex (PFC), but its specific effects on PFC neurons were unclear. Using slice electrophysiology in mice, researchers found that psilocin application onto layer 5 pyramidal neurons in the prelimbic PFC produced variable firing changes (increase, decrease, or no change) in unspecific neurons. However, in neurons identified as expressing 5-HT2ARs, psilocin consistently increased firing without altering synaptic transmission. The results demonstrate that psilocin evokes strong, 5-HT2AR- and Gαq-dependent firing changes in the PFC, offering insights into how psychedelics affect a brain region key to their therapeutic actions.

DOI: 10.1101/2022.11.15.516655 Full text Serotonergic Serotonin Infralimbic cortex Prefrontal cortex +7

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.

DOI: 10.1038/s41398-025-03611-0 Full text Neuroplasticity Prefrontal cortex Population Intracellular +11