Protocols to Induce, Prevent, and Treat Post-traumatic Stress Disorder-like Memory in Mice: Optogenetics and Behavioral Approaches

• Published in: Bio-protocol Vol. 11; no. 19; p. e4174
• Main Authors: Al Abed, Aline S, Sellami, Azza, Ducourneau, Eva-Gunnel, Bouarab, Chloé, Marighetto, Aline, Desmedt, Aline
• Format: Journal Article
• Language: English
• Published: United States Bio-Protocol 05-10-2021; Bio-protocol LLC
• Subjects: Biology; Methods; PTSD; Mouse; Corticosterone; Emotional hypermnesia; Traumatic memory; Contextual amnesia; Hippocampus; Fear conditioning
• ISSN: 2331-8325; 2331-8325
• DOI: 10.21769/BioProtoc.4174

One of the cardinal features of post-traumatic stress disorder (PTSD) is a paradoxical memory alteration including both
for salient trauma-related cues and
for the surrounding traumatic context. Interestingly, some clinical studies have suggested that contextual amnesia would causally contribute to the PTSD-related hypermnesia insofar as decontextualized, traumatic memory is prone to be reactivated in contexts that can be very different from the original traumatic context. However, most current animal models of PTSD-related memory focus exclusively on the emotional hypermnesia,
, the persistence of a strong fear memory, and do not distinguish normal (adaptive) from pathological (PTSD-like) fear memory, leaving unexplored the hypothetical critical role of contextual amnesia in PTSD-related memory formation, and thus challenging the development of innovative treatments. Having developed the first animal model that precisely recapitulates the two memory components of PTSD in mice (emotional hypermnesia and contextual amnesia), we recently demonstrated that contextual amnesia, induced by optogenetic inhibition of the hippocampus (dorsal CA1), is a causal cognitive process of PTSD-like hypermnesia formation. Moreover, the hippocampus-dependent contextualization of traumatic memory, by optogenetic activation of dCA1 in traumatic condition, prevents PTSD-like hypermnesia formation. Finally, once PTSD-like memory has been formed, the re-contextualization of traumatic memory by its reactivation in the original traumatic context normalizes this pathological fear memory. Revealing the key role of contextual amnesia in PTSD-like memory, this procedure opens a therapeutic perspective based on trauma contextualization and the underlying hippocampal mechanisms.