Psilocybin-enhanced fear extinction linked to bidirectional modulation of cortical ensembles.
Nature neuroscience June 1, 2025 Sophie A Rogers, Elizabeth A Heller, Gregory Corder 8 citations
A single dose of psilocybin enhances behavioral flexibility by altering neural activity in the retrosplenial cortex. Using longitudinal single-cell calcium imaging in mice during a 5-day trace fear learning and extinction assay, the study found that psilocybin suppressed fear-active neurons and recruited extinction-active neurons, a pattern that predicted improved fear extinction. A computational model showed that inhibiting simulated fear-active units modulated the recruitment of extinction-active units and behavioral variability in freezing, consistent with the experimental findings. These results suggest psilocybin promotes behavioral flexibility by reorganizing cortical ensembles in the retrosplenial cortex.