LOOKING FOR THE ENGRAM UNDERLYING PTSD-LIKE MEMORY: FOCUS ON THE ROLE OF THE ANTERIOR CINGULATE CORTEX AND NMDA RECEPTORS IN TRAUMATIC MEMORY MAINTENANCE

The engram that supports normal fear memory has been well studied, but the one supporting pathological memories remains elusive. Using a behavioral paradigm in mice that mimics the paradoxical memory impairment of post-traumatic stress disorder (PTSD), namely hypermnesia for a salient but irrelevant trauma-related cue and contextual amnesia for the traumatic context, and whole brain cFos mapping, we sought to identify the network and engram that support maladaptive and adaptive memories. First, we found a decorrelation of the functional connectome in PTSD-like memory compared to normal fear memory. Additionally, the anterior cingulate cortex (ACC) was shown to be hyperactivated after trauma encoding while during retrieval, the ACC and basolateral amygdala (BLA) showed increased reactivation, which positively correlated with PTSD memory impairments. Chemogenetically silencing ACC engram cells before retrieval completely disrupts the pathological memory expression. We additionally show that this traumatic memory is resistant to extinction and unable to reconsolidate, probably due to an inability to destabilize. Once recalled, memories enter a period of malleability, called destabilizationreconsolidation, during which they can be either reinforced or updated to change adaptively. Targeting the reconsolidation process could be a potential treatment for alleviating memories associated with conditions such as PTSD. Since NMDARs are identified as key players in memory lability upon reactivation, we hypothesized that GluN2B-containing NMDARs are required to initiate the plasticity process destabilizing normal fear memory. Here, we showed that reducing GluN2A activity in ACC of PTSD-like mice before memory reactivation can promote memory malleability and allow reconsolidation of traumatic memory.