5-HT2A receptors in layer 5 pyramidal neurons mediate the neuroplastic but not the hallucinogenic effects of psilocybin

Nature Neuroscience, Published online: 15 October 2026; doi:10.1038/s41593-026-02490-y

Psilocybin promotes and stabilizes new connections between neurons in the mouse cerebral cortex, especially after stress. Baker et al. show that 5-HT2A receptor signaling in layer 5 pyramidal neurons mediates this effect but is not required for a mouse behavioral proxy of hallucinations.