TY - JOUR
T1 - AMPA receptor exchange underlies transient memory destabilization on retrieval
AU - Hong, Ingie
AU - Kim, Jeongyeon
AU - Kim, Jihye
AU - Lee, Sukwon
AU - Ko, Hyoung Gon
AU - Nader, Karim
AU - Kaang, Bong Kiun
AU - Tsien, Richard W.
AU - Choi, Sukwoo
PY - 2013/5/14
Y1 - 2013/5/14
N2 - 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.
AB - 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.
KW - Fear conditioning
KW - Labile memory
KW - Memory reactivation
KW - Transient memory deconsolidation
UR - http://www.scopus.com/inward/record.url?scp=84877849388&partnerID=8YFLogxK
U2 - 10.1073/pnas.1305235110
DO - 10.1073/pnas.1305235110
M3 - Article
C2 - 23630279
AN - SCOPUS:84877849388
SN - 0027-8424
VL - 110
SP - 8218
EP - 8223
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 20
ER -