DECIPHERING THE CONTRIBUTION OF ADULT NEUROGENESIS TO RESILIENCE / VULNERABILITY TO DEVELOP A PTSD PHENOTYPE FOLLOWING PRENATAL STRESS EXPOSURE IN MICE

Prenatal stress (PS) is a major risk factor for psychiatric disorders, yet exposure to PS does not uniformly lead to pathology. Using a rodent model, we have shown that PS induces post-traumatic stress disorder (PTSD)-like memory deficits in only a subset of mice, highlighting the existence of resilience and vulnerability mechanisms. We hypothesize that vulnerability to PS arises from an alteration of adult-born granule neurons (DGNs) in the dentate gyrus of the hippocampus, a key structure for emotional memory. As these neurons were previously involved in pathological fear memory, disruptions in their number, activity, or connectivity may impact stress-related outcomes. Experiments were performed in F1 offspring of C57BL/6N females and 129S2 males. Pregnant females were exposed to daily restraint stress sessions from gestational day twelve until parturition. In adulthood, mice were exposed to a trauma -restraint stress followed by foot-shocks-, and behavioral consequences were assessed using a battery of tests evaluating core PTSD-like symptoms: fear memory, avoidance, hyperarousal, anxiety and anhedonia. Behavioral outcomes were integrated using z-score normalization to generate a PTSD-like score, allowing classification of PS mice as vulnerable or resilient. Ongoing analysis will determine whether levels of adult neurogenesis differ between these phenotypes. Overall, our study establishes the existence of interindividual differences in the propensity of mice to develop a pathological behavior after a combination of stressors. Comparison of adult neurogenesis levels in vulnerable and resilient animals will provide us with information regarding their contribution, which, in a later stage, can be compared to that of developmentally-born neurons.