ArticlebioRxiv : the preprint server for biology2024
Psilocybin-enhanced fear extinction linked to bidirectional modulation of cortical ensembles.
Article in bioRxiv : the preprint server for biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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3 authors at 2 institutions in 1 country.
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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 fear- and extinction- active 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.
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