title: On the resilience of remote traumatic memories against exposure therapy-mediated attenuation.
abstract: How to attenuate traumatic memories has long been the focus of intensive research efforts, as traumatic memories are extremely persistent and heavily impinge on the quality of life. Despite the fact that traumatic memories are often not readily amenable to immediate intervention, surprisingly few studies have investigated treatment options for remote traumata in animal models. The few that have unanimously concluded that exposure therapy-based approaches, the most successful behavioral intervention for the attenuation of recent forms of traumata in humans, fail to effectively reduce remote fear memories. Here, we provide an overview of these animal studies with an emphasis on why remote traumatic memories might be refractory to behavioral interventions: A lack of neuroplasticity in brain areas relevant for learning and memory emerges as a common denominator of such resilience. We then outline the findings of a recent study in mice showing that by combining exposure therapy-like approaches with small molecule inhibitors of histone deacetylases (HDACis), even remote memories can be persistently attenuated. This pharmacological intervention reinstated neuroplasticity to levels comparable to those found upon successful attenuation of recent memories. Thus, HDACis-or any other agent capable of heightening neuroplasticity-in conjunction with exposure therapy-based treatments might constitute a promising approach to overcome remote traumata.
authors.affiliation: Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA, USA lhtsai@mit.edu johannes.graeff@epfl.ch.
authors.forename: Li-Huei
authors.initials: LH
authors.lastname: Tsai
authors.affiliation: Brain Mind Institute, School of Life Sciences Ecole Polytechnique Fédérale Lausanne (EPFL), Lausanne, Switzerland lhtsai@mit.edu johannes.graeff@epfl.ch.
authors.forename: Johannes
authors.initials: J
authors.lastname: Gräff
mesh_terms: D000223:Adaptation, Psychological; D000818:Animals; D015928:Cognitive Behavioral Therapy; D003131:Combined Modality Therapy; D004195:Disease Models, Animal; D005239:Fear; D056572:Histone Deacetylase Inhibitors / Q000627:therapeutic use; D006801:Humans; D057567:Memory, Long-Term; D009473:Neuronal Plasticity; D055500:Resilience, Psychological; D013313:Stress Disorders, Post-Traumatic / Q000523:psychology / Q000628:therapy*
chemical_list: D056572:Histone Deacetylase Inhibitors
keywords: epigenetic; extinction; fear; histone acetylation; remote memories