The role of time-dependent memory processes in the development of PTSD-like symptoms in mice

The primary symptoms of Posttraumatic stress disorder (PTSD) were traditionally interpreted as an extraordinary strong memory of the trauma and hyperarousal, with the latter increasing with the passage of time (fear incubation) and evolving into generalized fear and generalized avoidance behaviour. Here we studied time-dependent changes in intensity and specificity of associative fear, as well as hyperarousal levels and avoidance behaviour in our mouse model of PTSD. Testing the animals at different time points after trauma, we observed a consistent level of conditioned fear and hyperarousal. On the other hand, context discrimination ratio decreased over time, whereas generalization of avoidance behaviour increased. Based on these time-dependent changes in the development of PTSD-like symptoms, we assumed that they might be differentially affected by early vs. late extinction training. Both early and late extinction training led to a long-lasting reduction of contextual and generalized fear, but indeed only early extinction caused an amelioration of hyperarousal and went ahead without spontaneous recovery of contextual fear. Taken together our data indicate that (i) fear incubation and generalized avoidance phenomena are not a result of an increase in hyperarousal, but a time-dependent reduction in recalling the details of trauma context, (ii) hyperarousal is largely independent of associative fear and relatively stable over time, (iii) early and late post-trauma extinction training might represent two qualitatively different processes and (iv) early post-trauma intervention is particularly important in order to prevent the development of long-lasting trauma-associated memories and hyperarousal.