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5-HT2A receptors in layer 5 pyramidal neurons mediate the neuroplastic but not the hallucinogenic effects of psilocybin
Published Web Location
https://doi.org/10.1038/s41593-026-02490-yAbstract
It is unclear how serotonin 2A receptors (5-HT2ARs) in cortical layer 5 pyramidal neurons differentially contribute to psilocybin-induced hallucinations versus neuroplasticity. Here we show that psilocybin promotes synapse formation and maturation while accelerating the elimination of pre-existing synapses. Cell type-specific manipulation further demonstrated that 5-HT2AR signaling in cortical layer 5 pyramidal neurons is necessary and sufficient for psilocybin-induced synaptic remodeling but dispensable for the head-twitch response, a rodent proxy of hallucination.
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