Time-dependent alterations in the medial prefrontal cortex after exposure to a traumatic stress in mice

Traumatic events that represent a threat for the subject’s life, can alter the systems involved in stress response, eventually leading to the development of pathological conditions such as post traumatic stress disorder (PTSD). A large body of evidence highlights structural and functional changes in several brain regions following traumatic events, however the dynamics of the neural circuit involved is not completely understood. The predator exposure model of traumatic stress has proven to induce long lasting effects on anxious behaviour in mice. Taking advantage of this model, we investigated stress-induced alterations in the activity of subregions of the medial prefrontal cortex and their input/output connections in hippocampus, amygdala and thalamus. Briefly, CD1 mice were subjected to a single 10-minute exposure to a rat in a familiar context, protected from direct attack and injury. After 14 stress-free days, anxious behaviour was assessed by EPM. The expression of the immediate early gene Fos was quantified at two different time points (1h and 14d after exposure), and used as marker of neural activation. Immunohistochemical analysis showed that at an early time point, activation of PL and IL mPFC was higher in exposed mice compared to controls. Interestingly, 14d later, stressed mice showed significantly lower Fos expression in PL cortex. Moreover, CA1-CA3 regions of dHC showed a selective reduction of activity 14d after stress. We are currently evaluating whether these activity changes could account for long-lasting pathological reactions to traumatic stress by chemogenetic techniques.