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

P. Rao-Ruiz, D.C. Rotaru, R.J. Loo, H.D. Mansvelder, O. Stiedl, A.B. Smit, S. Spijker

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

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. © 2011 Nature America, Inc. All rights reserved.
Original languageEnglish
Pages (from-to)1302-1308
Number of pages6
JournalNature Neuroscience
Volume14
Issue number10
DOIs
Publication statusPublished - 2011

Fingerprint

Dive into the research topics of 'Retrieval-specific endocytosis of GluA2-AMPARs underlies adaptive reconsolidation of contextual fear'. Together they form a unique fingerprint.

Cite this