Individual behavioral signatures shape processing of context-dependent social fear

Parapera Papantoniou, L.; Contestabile, A.; Prouvot Bouvier, P.-H.; Bezzola, C.; Lucchini, M.; Pfister, C.; Vityk, O.; Alazmi, B.; Tzanoulinou, S.

doi:10.64898/2026.10.05.754998

bioRxiv · 10.64898/2026.10.05.754998

Individual behavioral signatures shape processing of context-dependent social fear

Parapera Papantoniou, L.·Contestabile, A.·Prouvot Bouvier, P.-H.·Bezzola, C.·Lucchini, M.·Pfister, C.·Vityk, O.·Alazmi, B.·Tzanoulinou, S.

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Abstract

Context processing is an essential function in the cognitive repertoire of numerous species, including humans and mice, allowing them to learn from their environment and adapt their future behavior. Impairments or alterations in context processing are hypothesized to represent one of the core etiological mechanisms underlying trauma- and stressor-related disorders such as post-traumatic stress disorder (PTSD). Individual behavioral traits are key determinants of post-stress responses; however, how they influence distinct phases of contextual encoding and processing remains incompletely understood. This knowledge gap is further exacerbated by the limited availability of contextual fear protocols based on social stress, even though the latter is among the most frequent and impactful forms of stress exposure. Here, based on social defeat paradigms, we establish a longitudinal social conditioned place aversion (sCPA) protocol that leads to avoidance of the defeat-associated chamber in adult male mice. Prior characterization of mice according to anxiety-related phenotypes revealed that mice displaying high novelty-induced thigmotaxic (i.e. high anxiety-like) behavior showed lasting long-term memory of the defeat-associated chamber as denoted by persistent avoidance. On the other hand, lower levels of exploration/locomotor behaviors prior to stress exposure predicted greater avoidance of the defeat-associated chamber in the short-term. Finally, we reveal that inhibiting the activity of VTAVgat neurons during conditioning sessions abolished sCPA acquisition, while disrupting the predictive ability of locomotor/exploratory profiles derived prior to the sCPA. Our data establishes a robust temporally structured social stress-based conditioning protocol and reveals how prior individual anxiety- and exploration/locomotion-related traits influence distinct stages of context processing.

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Parapera Papantoniou, L., Contestabile, A., Prouvot Bouvier, P.-H., Bezzola, C., Lucchini, M., Pfister, C., Vityk, O., Alazmi, B., Tzanoulinou, S.. 2026-10-12. Individual behavioral signatures shape processing of context-dependent social fear. https://doi.org/10.64898/2026.10.05.754998

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