From threat perception to PTSD phenotypes: behavioral repertoire of mice in threat memories

Post-Traumatic Stress Disorder (PTSD) is characterized by exacerbated threat responses related and unrelated to a traumatic experience. Contextual threat conditioning (CTC) is a well-established animal model based on the association of a neutral stimulus with an aversive one, leading to a threat memory. In PTSD, these memories exhibit pathological features —hypermnesia, overgeneralization and deficits in extinction and extinction retention— that differentiate them from non-pathological ones. Predatory Imminence Continuum (PIC) hypothesis proposes that animals display a behavioral repertoire considering a low, medium and high threat perception state. Considering this, CTC was conducted in male and female mice with different electroshock intensities —a “high threat” 0.60 mA and a “low threat” 0.10 mA—. Behaviorally, we assessed the acquisition, recall, generalization and extinction of the threat memory. By quantifying freezing, rearing, jumping, grooming, tail rattling and locomotion, minute per minute, a comprehensive individual behavioral profile across the entire experiment was described. Taking into account the PIC framework, group effects during each test were analyzed and individual responses were traced to delineate profiles of resilience and vulnerability, thereby enhancing the translational relevance of the model.