REACTIVATION OF TRAUMATIC MEMORY ENGRAMS IN A MOUSE MODEL OF EARLY-LIFE STRESS

Early-life adversity (ELA) is a leading risk factor for developing mental disorders such as depression or anxiety in adulthood. However, it remains unclear how the cellular substrate of traumatic memories associated with ELA evolves through life and can participate in its behavioral outcome. We used FosTRAP2 mice, in which neuronal activation results in the irreversible expression of the fluorescent reporter TdTomato, to map the neuronal populations recruited during exposure to juvenile social defeat (P21, jSD). To assess stability of behavioral consequences, we realized a social interaction test (SIT) one week (P36, adolescent stage) after stress or three times prior to brain tissue collection, at P36, P56, P75 and P96. At P36, jSD induced strong social avoidance. In adulthood (P96), two behavioral profiles emerged; 55% of mice no longer exhibited social avoidance, while 45% maintained persistent avoidance. The reactivation of TdTomato neurons was assessed via c-fos immunohistochemistry following SIT conducted one week (P36) or two and a half months (P96, adult stage) after stress. We then attempted to characterize brain-wide activity profiles associated with these phenotypes. This approach aims at understanding how memory traces of early-life psychosocial trauma correlate with behavior and identify neuronal signatures of resilience and susceptibility to ELA.