• Bart C J Dirven, Lennart van Melis, Teya Daneva, Lieke Dillen, Judith R Homberg, Tamas Kozicz, and Marloes J A G Henckens.
• Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition, and Behaviour, Radboud University Medical Centre, 6500 HB Nijmegen, The Netherlands; Department of Medical Imaging, Anatomy, Donders Institute for Brain, Cognition, and Behaviour, Radboud University Medical Centre, 6500 HB Nijmegen, The Netherlands.
• Neuroscience. 2024 Mar 5; 540: 8710287-102.

AbstractWhile the majority of the population is ever exposed to a traumatic event during their lifetime, only a fraction develops posttraumatic stress disorder (PTSD). Disrupted trauma memory processing has been proposed as a core factor underlying PTSD symptomatology. We used transgenic Targeted-Recombination-in-Active-Populations (TRAP) mice to investigate potential alterations in trauma-related hippocampal memory engrams associated with the development of PTSD-like symptomatology. Mice were exposed to a stress-enhanced fear learning paradigm, in which prior exposure to a stressor affects the learning of a subsequent fearful event (contextual fear conditioning using foot shocks), during which neuronal activity was labeled. One week later, mice were behaviorally phenotyped to identify mice resilient and susceptible to developing PTSD-like symptomatology. Three weeks post-learning, mice were re-exposed to the conditioning context to induce remote fear memory recall, and associated hippocampal neuronal activity was assessed. While no differences in the size of the hippocampal neuronal ensemble activated during fear learning were observed between groups, susceptible mice displayed a smaller ensemble activated upon remote fear memory recall in the ventral CA1, higher regional hippocampal parvalbuminneuronal density and a relatively lower activity of parvalbumininterneurons upon recall. Investigation of potential epigenetic regulators of the engram revealed rather generic (rather than engram-specific) differences between groups, with susceptible mice displaying lower hippocampal histone deacetylase 2 expression, and higher methylation and hydroxymethylation levels. These finding implicate variation in epigenetic regulation within the hippocampus, as well as reduced regional hippocampal activity during remote fear memory recall in interindividual differences in susceptibility to traumatic stress.Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.

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