Preventing and treating PTSD-like memory by trauma contextualization

Abstract

Post-traumatic stress disorder (PTSD) is characterized by emotional hypermnesia on which preclinical studies focus so far. While this hypermnesia relates to salient traumatic cues, partial amnesia for the traumatic context can also be observed. Here, we show in mice that contextual amnesia is causally involved in PTSD-like memory formation, and that treating the amnesia by re-exposure to all trauma-related cues cures PTSD-like hypermnesia. These findings open a therapeutic perspective based on trauma contextualization and the underlying hippocampal mechanisms.

Parvalbumin Interneuron Activity Underlies Vulnerability to Post-Traumatic Stress Disorder in Autism

“…To determine whether ASD is a risk factor for PTSD, we used the Contactin-associated protein 2 knock out ( Cntnap2 KO) mouse model, which replicates the core behavioral symptoms of ASD(2,9,10). We first assessed the ability of wild-type (WT) and Cntnap2 KO mice to form adaptive fear memory in a contextual fear conditioning paradigm, modified from a model of PTSD-like memory(11,12). This paradigm combines a tone unpaired to a mild electric foot-shock, thus making the conditioning context the only relevant predictor of the threat (Figure 1A) .…”

“…Despite the divergence observed in the activation levels of the amygdala and the mPFC, we uncovered a common pattern of activation, shared between the ASD and PTSD conditions: a hypoactivation of the hippocampus (Figure 2B) . The key function of the hippocampus in the generation of PTSD has been recently demonstrated and the lack of hippocampal activation has been shown to prevent the encoding of the context surrounding a stressful event, hence shifting the fear towards a salient, irrelevant cue associated with the trauma(12,13). Our results confirm the pivotal role of the hippocampus-dependent contextualization capacity in determining the nature of the memory formed ( i .…”

“…Recontextualization was performed as previously described (12). Briefly, two days after long-term testing (Day 23), mice were re-exposed to the tone cue in the conditioning context, without electric shock (Figure 3, Day 23).…”

“…We next examined the malleability of the pathological memory developed in ASD conditions. We used recontextualization (12), a behavior-based rehabilitation strategy, which has been suggested as a therapeutic strategy in PTSD patients (13). The protocol consists of re-exposing the Cntnap2 KO mice displaying longterm PTSD-like memory to the original tone in the conditioning context with no footshock (Figure 3A).…”

“…Together, these results demonstrate that pathological memory can be reshaped into adapted fear memory. By reactivating the traumatic memory in the original environment, recontextualization allows the re-allocation of trauma representation into specific context, thereby suppressing abnormal hypermnesia (12). While this is promising, one caveat for the implementation of this procedure in patients will arise from being able to identify the origin of the trauma.…”