Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2019 Jan;236(1):49-57.
doi: 10.1007/s00213-018-5086-2. Epub 2018 Oct 29.

Reconsolidation/destabilization, extinction and forgetting of fear memory as therapeutic targets for PTSD

Satoshi Kida  1   2
Affiliations
Review

Reconsolidation/destabilization, extinction and forgetting of fear memory as therapeutic targets for PTSD

Satoshi Kida. Psychopharmacology (Berl). 2019 Jan.

Abstract

Post-traumatic stress disorder (PTSD) is a psychiatric disorder associated with memories of traumatic experiences. Conditioned fear memory, a representative model of traumatic memories, is observed across species from lower to higher animals, including humans. Numerous studies have investigated the mechanisms of conditioned fear memory and have led to the identification of the underlying processes involved in fear memory regulation, including cellular and systems consolidation of fear conditioning, destabilization/reconsolidation and extinction after fear memory retrieval, and forgetting of fear memory. These studies suggested that mechanisms for fear memory regulation are shared by humans and other higher animals. Additionally, rodent studies have identified the mechanisms of fear memory at the molecular, cellular, and circuit levels. Findings from these studies in rodents have been applied to facilitate the development and improvement of PTSD intervention. For instance, reconsolidation and extinction of fear memories have been applied for PTSD treatment to improve prolonged exposure (PE) therapy, an effective psychotherapy for PTSD. Combination of medications weakening retrieved traumatic memory (e.g., by facilitating both destabilization and extinction) with PE therapy may contribute to improvement of PTSD. Interestingly, a recent study in mice identified forgetting of fear memory as another potential therapeutic target for PTSD. A better understanding of the mechanisms involved in fear memory processes is likely to facilitate the development of better treatments for PTSD. This review describes fear memory processes and their mechanisms and discusses the pros and cons of applying how this knowledge can be applied in the development of interventions for PTSD.

Keywords: Consolidation; Destabilization; Extinction; Fear memory; Forgetting; PTSD; Reconsolidation.

PubMed Disclaimer

Conflict of interest statement

The author declares that he has no conflict of interest.

Figures

Fig. 1
Fig. 1
Signal transduction pathways for fear memory regulation. Memory destabilization or extinction after retrieval requires the activation of NMDA receptors (NMDAR) as the starting point; subsequent activation of L-type voltage-gated calcium channels (LVGCC), endogenous cannabinoid receptors (CB1), calcineurin, and finally proteasome-dependent protein degradation occurs. On the other hand, memory consolidation, reconsolidation, and consolidation of extinction memory (long-term extinction) require activation of transcription factor CREB-mediated transcription through phosphorylation at serine 133 by the activation of extracellular signal-regulated kinase/MAP kinase (ERK), protein A kinase (PKA), and/or Ca2+/calmodulin-dependent protein kinase IV (CaMKIV), which are downstream factors from cAMP and Ca2+ signal transduction
Fig. 2
Fig. 2
Fear memory regulation and PTSD treatment strategies. Novel PTSD therapy methods that shorten the duration of exposure therapy by blocking reconsolidation of fear memory, or by facilitating fear memory extinction, are being developed
Fig. 3
Fig. 3
PTSD treatment strategies with fear memory forgetting as a target. a Forgetting of hippocampus-dependent fear memories is enhanced through increased hippocampal neurogenesis. b Remote memories that are hippocampus-independent could return into a hippocampus-dependent state through long-duration retrieval of fear memory by long re-exposure to the context for 10 min, and then forgetting of the remote memories can be promoted through hippocampal neurogenesis.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Abel T, Lattal KM. Molecular mechanisms of memory acquisition, consolidation and retrieval. Curr Opin Neurobiol. 2001;11:180–187. - PubMed
    1. Akers KG, Martinez-Canabal A, Restivo L, Yiu AP, De Cristofaro A, Hsiang HL, Wheeler AL, Guskjolen A, Niibori Y, Shoji H, Ohira K, Richards BA, Miyakawa T, Josselyn SA, Frankland PW. Hippocampal neurogenesis regulates forgetting during adulthood and infancy. Science. 2014;344:598–602. - PubMed
    1. Anagnostaras SG, Maren S, Fanselow MS. Temporally graded retrograde amnesia of contextual fear after hippocampal damage in rats: within-subjects examination. J Neurosci. 1999;19:106–1114. - PMC - PubMed
    1. Ben Mamou C, Gamache K, Nader K. NMDA receptors are critical for unleashing consolidated auditory fear memories. Nat Neurosci. 2006;9:1237–1239. - PubMed
    1. Bentz D, Michael T, de Quervain DJ, Wilhelm FH. Enhancing exposure therapy for anxiety disorders with glucocorticoids: from basic mechanisms of emotional learning to clinical applications. J Anxiety Disord. 2010;24:223–230. - PubMed

MeSH terms