AMPA receptor exchange underlies transient memory destabilization on retrieval

作者：Hong Ingie; Kim Jeongyeon; Kim Jihye; Lee Sukwon; Ko Hyoung Gon; Nader Karim; Kaang Bong Kiun; Tsien Richard W^*; Choi Sukwoo

来源：Proceedings of the National Academy of Sciences of the United States of America, 2013, 110(20): 8218-8223.

DOI：10.1073/pnas.1305235110

• fear conditioning
• memory reactivation
• transient memory deconsolidation
• labile memory

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.

• 出版日期2013-5-14