AMPA receptor exchange underlies transient memory destabilization on retrieval

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 110; no. 20; pp. 8218 - 8223
• Main Authors: Hong, Ingie, Kim, Jeongyeon, Kim, Jihye, Lee, Sukwon, Ko, Hyoung-Gon, Nader, Karim, Kaang, Bong-Kiuń, Tsien, Richard W., Choi, Sukwoo
• Format: Journal Article
• Language: English
• Published: Washington, DC National Academy of Sciences 14.05.2013; National Acad Sciences
• Subjects: AMPA receptors; Amygdala; Animals; Behavior, Animal; Behavioral neuroscience; Biological and medical sciences; Biological Sciences; Brain - pathology; Calcium - metabolism; Conditioning, Classical; Correlation analysis; Electrophysiology; Endocytosis; Fear - physiology; Fundamental and applied biological sciences. Psychology; Gene expression; Male; Memory; Memory - physiology; Memory recall; Neurons; Physiology; Post hoc; Rats; Rats, Sprague-Dawley; Recall; Receptors, AMPA - metabolism; Receptors, N-Methyl-D-Aspartate - metabolism; Synapses; Synapses - metabolism; Vehicles; Vertebrates: nervous system and sense organs; Fear; Memory retrieval; AMPA receptor; fear conditioning; Memory; Glutamate receptor; transient memory deconsolidation; Conditioning; labile memory; memory reactivation
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1305235110

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.