Retrieval-specific endocytosis of GluA2-AMPARs underlies adaptive reconsolidation of contextual fear

Nat Neurosci. 2011 Sep 11;14(10):1302-8. doi: 10.1038/nn.2907.


Upon retrieval, fear memories are rendered labile and prone to modification, necessitating a restabilization process of reconsolidation to persist further. This process is also crucial for modulating both strength and content of an existing memory and forms a promising therapeutic target for fear-related disorders. However, the molecular and cellular mechanism of adaptive reconsolidation still remains obscure. Here we show that retrieval of fear memory induces a biphasic temporal change in GluA2-containing AMPA-type glutamate receptor (AMPAR) membrane expression and synaptic strength in the mouse dorsal hippocampus. Blockade of retrieval-induced, regulated, GluA2-dependent endocytosis enhanced subsequent expression of fear. In addition, this blockade prevented the loss of fear response after reconsolidation-update of fear memory content in the long-term. Thus, endocytosis of GluA2-containing AMPARs allows plastic changes at the synaptic level that exerts an inhibitory constraint on memory strengthening and underlies the loss of fear response by reinterpretation of memory content during adaptive reconsolidation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptation, Physiological / drug effects
  • Adaptation, Physiological / physiology
  • Analysis of Variance
  • Animals
  • Anisomycin / pharmacology
  • Behavior, Animal
  • Biotinylation
  • Conditioning, Classical / drug effects
  • Conditioning, Classical / physiology*
  • Electroshock / adverse effects
  • Endocytosis / drug effects
  • Endocytosis / physiology*
  • Excitatory Postsynaptic Potentials / drug effects
  • Fear / drug effects
  • Fear / physiology*
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / physiology
  • Hippocampus / cytology
  • In Vitro Techniques
  • Male
  • Mental Recall / drug effects
  • Mental Recall / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Patch-Clamp Techniques
  • Peptides / pharmacology
  • Protein Synthesis Inhibitors / pharmacology
  • Protein Transport / drug effects
  • Receptors, AMPA / chemistry
  • Receptors, AMPA / metabolism*
  • Synapses / drug effects
  • Synapses / metabolism*
  • Time Factors


  • Peptides
  • Protein Synthesis Inhibitors
  • Receptors, AMPA
  • Anisomycin
  • glutamate receptor ionotropic, AMPA 1