한빛사 논문
Ingie Honga,1, Jeongyeon Kima,1, Jihye Kima,1, Sukwon Leea, Hyoung-Gon Koa,b, Karim Naderc, Bong-Kiun Kaanga,b, Richard W. Tsiend,2, and Sukwoo Choia,2
aSchool of Biological Sciences,
bDepartment of Brain and Cognitive Sciences, College of Natural Sciences, Seoul National University, Seoul 151-747, Korea;
cDepartment of Psychology, McGill University, Montreal, QC, Canada H3A 1B1; and
dDepartment of Physiology and Neuroscience, Neuroscience Institute, New York University Langone Medical Center, New York, NY 10016
Contributed by Richard W. Tsien, March 20, 2013 (sent for review February 3, 2013)
Footnotes
1I.H., Jeongyeon Kim, and Jihye Kim contributed equally to this work.
2To whom correspondence may be addressed.
Author contributions: I.H., Jeongyeon Kim, Jihye Kim, R.W.T., and S.C. designed research; I.H., Jeongyeon Kim, Jihye Kim, S.L., and H.-G.K. performed research; I.H., Jeongyeon Kim, Jihye Kim, R.W.T., and S.C. analyzed data; and I.H., Jeongyeon Kim, Jihye Kim, K.N., B.-K.K., R.W.T., and S.C. wrote the paper.
The authors declare no conflict of interest.
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.
This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1305235110/-/DCSupplemental.
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