Psilocybin-enhanced fear extinction linked to bidirectional modulation of cortical ensembles
OpenAlex – February 04, 2024
Source: OpenAlex
Summary
A single dose of psilocybin dramatically boosts behavioral flexibility. Neuroscience reveals this psychedelic compound, an alkaloid with Neurotransmitter Receptor Influence on Behavior, acutely suppresses fear-active neurons while later recruiting extinction-active neurons. Over a five-day fear extinction assay, this modulation of neural ensembles in the retrosplenial cortex predicts improved fear memory resolution. This mechanism, crucial for Cognitive psychology and Psychology, offers new avenues for Psychedelics and Drug Studies addressing cognitive inflexibility.
Abstract
Abstract The serotonin 2 receptor (5HT2R) agonist psilocybin displays rapid and persistent therapeutic efficacy across neuropsychiatric disorders characterized by cognitive inflexibility. However, the impact of psilocybin on patterns of neural activity underlying sustained changes in behavioral flexibility has not been characterized. To test the hypothesis that psilocybin enhances behavioral flexibility by altering activity in cortical neural ensembles, we performed longitudinal single-cell calcium imaging in the retrosplenial cortex across a five-day trace fear learning and extinction assay. A single dose of psilocybin induced ensemble turnover between fear learning and extinction days while oppositely modulating activity in fearand extinctionactive neurons. The acute suppression of fear-active neurons and delayed recruitment of extinction-active neurons were predictive of psilocybin-enhanced fear extinction. A computational model revealed that acute inhibition of fear-active neurons by psilocybin is sufficient to explain its neural and behavioral effects days later. These results align with our hypothesis and introduce a new mechanism involving the suppression of fear-active populations in the retrosplenial cortex.