Prochaine conférence du GDR le 6 Mai 2022 de 11h à 12h par Aline Desmedt (Neurocentre Magendie, Bordeaux)

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Preventing and treating PTSD-like memory by the hippocampus-dependent trauma contextualization

Post-traumatic stress disorder (PTSD) is characterized by a paradoxical memory alteration with hypermnesia for salient traumatic cues and amnesia for the traumatic context. Clinical studies strongly suggest that a deficit in trauma contextualization might be responsible for the formation of PTSD symptoms. Recovery from PTSD-related hypermnesia would thus depend on recovery from contextual amnesia. Yet, preclinical research have left unexplored the putative key role of a deficit in the hippocampus-dependent contextual memory in PTSD.

Using the first animal model that precisely recapitulates PTSD-related hypermnesia and amnesia in mice, we first show that compared to normal fear memory, PTSD-like fear memory is specifically associated with hippocampal hypoactivation, as well as cellular and molecular alterations such as dendritic atrophy, downregulation of the BDNF/MAPK signaling pathway and hypermethylation of histones in the dorsal hippocampus. Second, we show that optogenetic inhibition of the hippocampus (dCA1) during stress can produce PTSD-like memory, whereas activating the dCA1 prevents its formation. Third, once the PTSD-like memory is formed, recontextualizing this traumatic memory by evoking it in the original traumatic context restores a long-lasting normal fear memory. Finally, normalizing (i) the altered hippocampal neuropmorphology, (ii) the BDNF/MAPK pathway or (iii) the imbalance of the acetylation/methylation levels of H3K9 in the hippocampus promotes contextual memory of the trauma and prevents the formation of PTSD-like memory.

These findings indicate that PTSD-like memory depends on contextual amnesia and that normalizing the hippocampal activity at the system, cellular or molecular level underlies a switch from PTSD-like to normal fear memory via trauma contextualization. Therefore, these data call the therapeutic approaches of PTSD to turn to contextual amnesia and the underlying hippocampal dysfunction.

2 commentaires sur “Prochaine conférence du GDR le 6 Mai 2022 de 11h à 12h par Aline Desmedt (Neurocentre Magendie, Bordeaux)”

    1. Sorry about that, we change the zoom account and it had some consequences. But I hope everything has been fixed now

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