Prefrontal correlates of fear generalization during endocannabinoid depletion.

ABSTRACT: 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 in a childhood maltreatment-exposed and -nonexposed mixed population, combined with human and rodent fear-conditioning models. Here we show that 2-AG levels were inversely associated with fear generalization at the behavioral level in both mice and humans. In mice, 2-AG depletion increased the proportion of neurons that respond to, and the similarity of neuronal representations for, both threat-predictive and neutral stim

SUBMITTER: Rosas-Vidal LE 

PROVIDER: S-EPMC12126220 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature