5-HT(2A) receptors in layer 5 pyramidal neurons mediate the neuroplastic but not the hallucinogenic effects of psilocybin.

5-HT(2A) receptors in layer 5 pyramidal neurons mediate psilocybin-induced neuroplasticity but are not required for hallucinations in rodents.

• Why it matters: Understanding the distinct neural mechanisms underlying psilocybin's effects is crucial for developing targeted therapies that harness neuroplasticity without hallucinations.
• What they did: The study used cell type-specific manipulation to show that 5-HT(2A) receptor signaling in cortical layer 5 pyramidal neurons is necessary and sufficient for synaptic remodeling, involving synapse formation, maturation, and elimination, but not for the head-twitch response.
• The result: This indicates that 5-HT(2A) receptors in these neurons selectively mediate neuroplastic effects, enabling potential therapeutic strategies that separate neuroplasticity from hallucinogenic side effects.