Intra-amygdala metaplasticity modulation of fear extinction learning

Rinki Saha, Martin Kriebel, Rachel Anunu, Hansjuergen Volkmer, Gal Richter-Levin

Research output: Contribution to journalReview articlepeer-review


The amygdala is a key brain region involved in emotional memory formation. It is also responsible for memory modulation in other brain areas. Under extreme conditions, amygdala modulation may lead to the generation of abnormal plasticity and trauma-related psychopathologies. However, the amygdala itself is a dynamic brain region, which is amenable to long-term plasticity and is affected by emotional experiences. These alterations may modify the way the amygdala modulates activity and plasticity in other related brain regions, which in turn may alter the animal's response to subsequent challenges in what could be termed as “Behavioral metaplasticity.”Because of the reciprocal interactions between the amygdala and other emotion processing regions, such as the medial prefrontal cortex (mPFC) or the hippocampus, experience-induced intra-amygdala metaplasticity could lead to alterations in mPFC-dependent or hippocampus-dependent behaviors. While initiated by alterations within the basolateral amygdala (BLA), such alterations in other brain regions may come to be independent of BLA modulation, thus establishing what may be termed “Trans-regional metaplasticity.” In this article, we review evidence supporting the notions of intra-BLA metaplasticity and how this may develop into “Trans-regional metaplasticity.” Future research is needed to understand how such dynamic metaplastic alterations contribute to developing psychopathologies, and how this knowledge may be translated into promoting novel interventions in psychopathologies associated with fear, stress, and trauma.

Original languageEnglish
Pages (from-to)2455-2463
Number of pages9
JournalEuropean Journal of Neuroscience
Issue number9-10
StatePublished - May 2022

Bibliographical note

Funding Information:
The authors wish to thank the long list of students, postdocs, and colleagues, many of whom appear in the reference list, who were part of this long journey. The authors would like to thank Netta Richter‐Levin for English editing the paper. This research was supported by an Israel Science Foundation grant number 1517/16 to G.R.‐L. and by the State of Israel Ministry of Science & Technology grant number 3‐14356. The funding sources were not involved in the study.

Publisher Copyright:
© 2020 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.


  • GABA
  • PTSD
  • metaplasticity
  • neurofascin
  • stress

ASJC Scopus subject areas

  • Neuroscience (all)


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