Neural network alterations across time in a mouse model of traumatic stress

Neural network alterations across time in a mouse model of traumatic stress Tommaso Seri, Greta De Cicco, Andrea Mele, Arianna Rinaldi Department of Biology and Biotechnology "Charles Darwin" and Centre for Research in Neurobiology “Daniel Bovet”, Sapienza University of Rome, Rome, Italy PhD Programmein Behavioral Neuroscience, SapienzaUniversity of Rome, Rome, Italy The response to stress consists in a set of physiological and behavioural adaptations, aimed at coping with the challenges encountered by the individual. However, traumatic events that represent a threat for the subject’s life, could alter the circuits involved in stress response, eventually leading to pathological conditions, such as post-traumatic stress disorder (PTSD). Many studies highlight structural and functional changes in several brain regions following traumatic events, however the dynamics of the neural circuit involved, are not completely understood. We used the predator exposure model of traumatic stress, which has proven to induce long lasting effects on anxious behaviour in mice, to investigate stress-induced alterations in the activity of structures involved in stress response and reciprocally interconnected, such as subregions of the medial prefrontal cortex (mPFC), hippocampus, amygdala, and thalamus. CD1 mice were subjected to a single 10-minutes exposure to a rat in a familiar context, protected from direct attack and injury. After 13 stress-free days, anxious behaviour was assessed by elevated plus maze. Then, we evaluated neural activation 1h and 14d after predator exposure, using as activity marker the expression of the immediate early gene Fos. Immunohistochemical analysis of Fos levels showed an hyperactivation of BLA in exposed mice compared to controls at the early time point. Conversely, 14d later, stressed mice showed a general reduction of Fos expression, significant in PL and IL mPFC, as well as CA1-CA3 regions of dorsal hippocampus. We applied inter-regional correlation analysis and network connectivity graphs to explore how functional connections among structures of the circuit were altered by traumatic stress across time. Despite the lower magnitude of Fos expression, at the late time point the activity of the structures analysed was more tightly correlated than 1h after the traumatic event, suggesting a time dependent shift in functional connectivity induced by predator exposure.