Psilocybin-enhanced fear extinction linked to bidirectional modulation of cortical ensembles
bioRxiv (Cold Spring Harbor Laboratory) February 4, 2024 Sophie A. Rogers, Elizabeth A. Heller, Gregory Corder 11 citations preprint
A single dose of the serotonin 2 receptor agonist psilocybin enhances behavioral flexibility by altering neural activity in the retrosplenial cortex. In a five-day trace fear learning and extinction assay using longitudinal single-cell calcium imaging in mice, psilocybin induced ensemble turnover between fear learning and extinction days, oppositely modulating activity in fear- and extinction-active neurons. Acute suppression of fear-active neurons and delayed recruitment of extinction-active neurons predicted enhanced fear extinction. A computational model showed that acute inhibition of fear-active neurons by psilocybin suffices to explain its neural and behavioral effects days later, suggesting a new mechanism involving suppression of fear-active populations.