AMPA receptor exchange underlies transient memory destabilization on retrieval

Ingie Hong, Jeongyeon Kim, Jihye Kim, Sukwon Lee, Hyoung Gon Ko, Karim Nader, Bong Kiun Kaang, Richard W. Tsien, Sukwoo Choi

Research output: Contribution to journalArticlepeer-review

Abstract

A consolidated memory can be transiently destabilized by memory retrieval, after which memories are reconsolidated within a few hours; however, the molecular substrates underlying this destabilization process remain essentially unknown. Here we show that at lateral amygdala synapses, fear memory consolidation correlates with increased surface expression of calcium-impermeable AMPA receptors (CI-AMPARs), which are known to be more stable at the synapse, whereas memory retrieval induces an abrupt exchange of CI-AMPARs to calcium-permeable AMPARs (CP-AMPARs), which are known to be less stable at the synapse. We found that blockade of either CI-AMPAR endocytosis or NMDA receptor activity during memory retrieval, both of which blocked the exchange to CP-AMPARs, prevented memory destabilization, indicating that this transient exchange of AMPARs may underlie the transformation of a stable memory into an unstable memory. These newly inserted CP-AMPARs gradually exchanged back to CI-AMPARs within hours, which coincided with the course of reconsolidation. Furthermore, blocking the activity of these newly inserted CP-AMPARs after retrieval impaired reconsolidation, suggesting that they serve as synaptic 'tags' that support synapse-specific reconsolidation. Taken together, our results reveal unexpected physiological roles of CIAMPARs and CP-AMPARs in transforming a consolidated memory into an unstable memory and subsequently guiding reconsolidation.

Original languageEnglish (US)
Pages (from-to)8218-8223
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume110
Issue number20
DOIs
StatePublished - May 14 2013
Externally publishedYes

Keywords

  • Fear conditioning
  • Labile memory
  • Memory reactivation
  • Transient memory deconsolidation

ASJC Scopus subject areas

  • General

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