Activity-Dependent Neural Rewiring by Psilocybin: A Monosynaptic Rabies Virus Tracing Study
Zenodo (CERN European Organization for Nuclear Research) February 6, 2026 Zen Revista
Psilocybin, the psychoactive compound in magic mushrooms, triggers network-specific neural rewiring that is activity-dependent and programmable. Using genetically modified rabies virus for monosynaptic circuit tracing, researchers discovered that psilocybin strengthens sensory-motor pathways while weakening cortical-cortical feedback loops linked to rumination and depression. Sensory regions showed up to 10% increases in connectivity, and self-referential regions exhibited up to 15% decreases. Neural activity during the psilocybin window determines which circuits are strengthened or weakened, suggesting therapeutic interventions could be optimized by controlling sensory and cognitive experiences during treatment. These findings provide mechanistic insights into psilocybin’s rapid antidepressant effects.