title: AMPA receptor exchange underlies transient memory destabilization on retrieval.
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 CI-AMPARs and CP-AMPARs in transforming a consolidated memory into an unstable memory and subsequently guiding reconsolidation.
authors: School of Biological Sciences, Seoul National University, Seoul 151-747, Korea.
authors: Ingie
authors: I
authors: Hong
authors: Jeongyeon
authors: J
authors: Kim
authors: Jihye
authors: J
authors: Kim
authors: Sukwon
authors: S
authors: Lee
authors: Hyoung-Gon
authors: HG
authors: Ko
authors: Karim
authors: K
authors: Nader
authors: Bong-Kiun
authors: BK
authors: Kaang
authors: Richard W
authors: RW
authors: Tsien
authors: Sukwoo
authors: S
authors: Choi
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D001921:Brain / Q000473:pathology; D002118:Calcium / Q000378:metabolism; D003214:Conditioning, Classical; D004594:Electrophysiology; D004705:Endocytosis; D005239:Fear / Q000502:physiology; D008297:Male; D008568:Memory / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D013569:Synapses / Q000378:metabolism
chemical_list: D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D002118:Calcium
keywords: fear conditioning; labile memory; memory reactivation; transient memory deconsolidation
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