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Team “Pathophysiology of declarative memory”
The hippocampus at the core of PTSD-like memory
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 would leave traumatic memory out of control and thus prone to be automatically reactivated upon trauma-related cues in any context through flashbacks. In this view, recovery from PTSD-related hypermnesia would thus depend on recovery from contextual amnesia. Yet, preclinical research focuses exclusively on the emotional hypermnesia, leaving unexplored the putative causal role of a deficit in the hippocampus-dependent trauma contextualization in PTSD.
Using the first animal model that precisely recapitulates PTSD-related hypermnesia and amnesia, we first show that compared to normal fear memory, PTSD-like fear memory is specifically associated with hippocampal hypoactivation and neuronal alterations. Second, we show that optogenetic inhibition of the hippocampus (dCA1) during stress can produce PTSD-like memory in mice, whereas activating the dCA1 prevents its formation and promotes normal contextual fear memory. Finally, trauma re-contextualization normalizes PTSD-like memory, promoting the expression of a long-lasting normal fear memory.
These findings indicate that PTSD-like memory depends on contextual amnesia and that promoting the hippocampal function promotes a switch from PTSD-like to normal fear memory via trauma contextualization. Therefore, these data call for promoting therapeutic approaches of PTSD centered on trauma contextualization and its underlying hippocampal mechanisms.