Longevity & AgingPsilocybin Rewires Brain Networks Through Activity-Dependent Synaptic Plasticity
Researchers used monosynaptic rabies virus tracing in mice to map how a single psilocybin dose (1 mg/kg) reorganizes brain-wide inputs to two major frontal cortical neuron subtypes. They found psilocybin strengthens connections from sensorimotor, visual, and medial (default-mode-like) networks while weakening inputs from recurrent cortico-cortical loops and the lateral network. Crucially, this rewiring depended on drug-evoked spiking activity: silencing a presynaptic region during psilocybin administration blocked the plasticity. The findings reveal a network-specific, activity-dependent mechanism by which a single psychedelic dose can produce lasting structural changes, potentially explaining psilocybin's durable antidepressant effects despite its short half-life.
