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BIOLOGICAL SCIENCES / NEUROSCIENCE
Amygdala depotentiation and fear extinction

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

*School of Biological Sciences, College of Natural Sciences, Seoul National University, Seoul 151-742, Korea; Departments of Biology and Biological and Nanopharmaceutical Sciences, Kyunghee University, Seoul 130-701, Korea; Department of Anatomy, Division of Brain Korea 21 Biomedical Science, College of Medicine, Korea University, Seoul 136-701, Korea; and Department of Biological Sciences, College of Natural Sciences, Inha University, 253 Yong-Hyun Dong, Nam-Gu, Inchon 402-751, Korea

Communicated by Richard W. Tsien, Stanford University School of Medicine, Stanford, CA, November 13, 2007 (received for review June 6, 2007)

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.

lateral amygdala | fear conditioning | AMPA receptor | endocytosis

The authors declare no conflict of interest.

This article contains supporting information online at www.pnas.org/cgi/content/full/0710548105/DC1.

^¶To whom correspondence may be addressed. E-mail: sukwoo12{at}snu.ac.kr or kisoon_shin{at}khu.ac.kr

© 2007 by The National Academy of Sciences of the USA

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