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.
Highlights
Post-traumatic stress disorder (PTSD) is characterized by emotional hypermnesia on which preclinical studies focus so far
Mice received a bilateral injection of AAV5-expressing ArchT or ChR2 into the dorsal CA1, and received chronic bilateral optic fiber implants. dCA1 was targeted because (i) it was previously shown to be hypoactivated in mice developing PTSD-like memory compared to those expressing normal fear memory[15] and (ii) it is classically described as a key hippocampal subfield for both contextual and declarative memory[17,18]
In control animals that were not submitted to optogenetic stimulation during conditioning (Day 1), memory tests (Day 2) confirmed our previous findings[15]: CORT-injected mice displayed PTSD-like alterations of fear memory with an abnormal fear response to the tone and decreased fear to the context (Fig. 1a, top)
Summary
Post-traumatic stress disorder (PTSD) is characterized by emotional hypermnesia on which preclinical studies focus so far. PTSD patients experience recurrent and intrusive recollection of traumatic memories characterized by intense fear responses in ordinary, safe situations (i.e. emotional hypermnesia), while having difficulties retrieving exhaustive narrative (i.e. declarative) memories of their trauma, as certain aspects of the context are missing[1,2,3,4,5,6] This contextual amnesia, believed to result from hippocampal hypofunction induced by intense stress[7,8,9,10,11,12,13], is most frequently partial, and even very discreet sometimes. In parallel, when reexposed to the conditioning context alone (i.e., Context test), CORT-injected mice display a reduced fear response to the conditioning context that reveals a contextual amnesia Using this model, we tested the hypothesis that contextual amnesia is causally involved in PTSD-like memory by manipulating contextual memory formation through optogenetic inhibition/activation of the hippocampus. We tested whether hippocampal inhibition during conditioning, that should impair context memorization, promotes the formation of PTSD-like memory in Vehicle (Veh)-injected mice, whereas hippocampal activation, expected to promote context memorization, may prevent PTSD-like memory in CORT-injected mice
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