{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T20:39:07Z","timestamp":1768509547142,"version":"3.49.0"},"posted":{"date-parts":[[2024,1,30]]},"group-title":"Neuroscience","reference-count":72,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,1,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Maladaptive fear generalization is one of the hallmarks of trauma-related disorders. The endocannabinoid 2-arachidonoylglycerol (2-AG) is crucial for modulating anxiety, fear, and stress adaptation but its role in balancing fear discrimination versus generalization is not known. To address this, we used a combination of plasma endocannabinoid measurement and neuroimaging from a childhood maltreatment exposed and non-exposed mixed population combined with human and rodent fear conditioning models. Here we show that 2-AG levels are inversely associated with fear generalization at the behavioral level in both mice and humans. In mice, 2-AG depletion increases the proportion of neurons, and the similarity between neuronal representations, of threat-predictive and neutral stimuli within prelimbic prefrontal cortex ensembles. In humans, increased dorsolateral prefrontal cortical-amygdala resting state connectivity is inversely correlated with fear generalization. These data provide convergent cross-species evidence that 2-AG is a key regulator of fear generalization and suggest 2-AG deficiency could represent a trauma-related disorder susceptibility endophenotype.<\/jats:p>","DOI":"10.1101\/2024.01.30.577847","type":"posted-content","created":{"date-parts":[[2024,1,30]],"date-time":"2024-01-30T23:20:26Z","timestamp":1706656826000},"source":"Crossref","is-referenced-by-count":2,"title":["PREFRONTAL CORRELATES OF FEAR GENERALIZATION DURING ENDOCANNABINOID DEPLETION"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9849-0161","authenticated-orcid":false,"given":"Luis E.","family":"Rosas-Vidal","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saptarnab","family":"Naskar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leah 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