On the resilience of remote traumatic memories against exposure therapy-mediated attenuation


  • Li-Huei Tsai,

    Corresponding author
    1. Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA
    2. Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA, USA
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  • Johannes Gräff

    Corresponding author
    1. Brain Mind Institute, School of Life Sciences, Ecole Polytechnique Fédérale Lausanne (EPFL), Lausanne, Switzerland
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  • See also Glossary for abbreviations used in this article.


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.