Dissociating the Hallucinogenic and Neuroplastic Effects of Psilocybin
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It is unclear how serotonin 2A receptors (5-HT 2A Rs) in cortical layer 5 pyramidal neurons (L5 PyrNs) differentially contribute to psilocybin-induced hallucinations versus neuroplasticity. Our longitudinal in vivo imaging revealed that psilocybin promotes new synapse formation and maturation while accelerating the elimination of pre-existing synapses. Cell type-specific manipulation of 5-HT 2A R expression in L5 PyrNs further demonstrated that it is necessary and sufficient for psilocybin-induced neuroplasticity but dispensable for hallucinations.
