Amygdala depotentiation and fear extinction

Jeongyeon Kim, Sukwon Lee, Kyungjoon Park, Ingie Hong, Beomjong Song, Gihoon Son, Heewoo Park, Ryoung Kim Woon, Eunjin Park, Kyung Choe Han, Hyun Kim, Changjoong Lee, Woong Sun, Kyungjin Kim, Soon Shin Ki, Sukwoo Choi

Research output: Contribution to journalArticle

174 Citations (Scopus)

Abstract

Auditory fear memory is thought to be maintained by fear conditioning-induced potentiation of synaptic efficacy, which involves enhanced expression of surface AMPA receptor (AMPAR) at excitatory synapses in the lateral amygdala (LA). Depotentiation, reversal of conditioning-induced potentiation, has been proposed as a cellular mechanism for fear extinction; however, a direct link between depotentiation and extinction has not yet been tested. To address this issue, we applied both ex vivo and in vivo approaches to rats in which fear memory had been consolidated. A unique form of depotentiation reversed conditioning-induced potentiation at thalamic input synapses onto the LA (T-LA synapses) ex vivo. Extinction returned the enhanced T-LA synaptic efficacy observed in conditioned rats to baseline and occluded the depotentiation. Consistently, extinction reversed conditioning-induced enhancement of surface expression of AMPAR subunits in LA synaptosomal preparations. A GluR2-derived peptide that blocks regulated AMPAR endocytosis inhibited depotentiation, and microinjection of a cell-permeable form of the peptide into the LA attenuated extinction. Our results are consistent with the use of depotentiation to weaken potentiated synaptic inputs onto the LA during extinction and provide strong evidence that AMPAR removal at excitatory synapses in the LA underlies extinction.

Original languageEnglish
Pages (from-to)20955-20960
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number52
DOIs
Publication statusPublished - 2007 Dec 26

Keywords

  • AMPA receptor
  • Endocytosis
  • Fear conditioning
  • Lateral amygdala

ASJC Scopus subject areas

  • General

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  • Cite this

    Kim, J., Lee, S., Park, K., Hong, I., Song, B., Son, G., Park, H., Woon, R. K., Park, E., Han, K. C., Kim, H., Lee, C., Sun, W., Kim, K., Ki, S. S., & Choi, S. (2007). Amygdala depotentiation and fear extinction. Proceedings of the National Academy of Sciences of the United States of America, 104(52), 20955-20960. https://doi.org/10.1073/pnas.0710548105