title: Amygdala depotentiation and fear extinction.
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.
authors.affiliation: School of Biological Sciences, College of Natural Sciences, Seoul National University, Seoul 151-742, Korea.
authors.forename: Jeongyeon
authors.initials: J
authors.lastname: Kim
authors.forename: Sukwon
authors.initials: S
authors.lastname: Lee
authors.forename: Kyungjoon
authors.initials: K
authors.lastname: Park
authors.forename: Ingie
authors.initials: I
authors.lastname: Hong
authors.forename: Beomjong
authors.initials: B
authors.lastname: Song
authors.forename: Gihoon
authors.initials: G
authors.lastname: Son
authors.forename: Heewoo
authors.initials: H
authors.lastname: Park
authors.forename: Woon Ryoung
authors.initials: WR
authors.lastname: Kim
authors.forename: Eunjin
authors.initials: E
authors.lastname: Park
authors.forename: Han Kyung
authors.initials: HK
authors.lastname: Choe
authors.forename: Hyun
authors.initials: H
authors.lastname: Kim
authors.forename: Changjoong
authors.initials: C
authors.lastname: Lee
authors.forename: Woong
authors.initials: W
authors.lastname: Sun
authors.forename: Kyungjin
authors.initials: K
authors.lastname: Kim
authors.forename: Ki Soon
authors.initials: KS
authors.lastname: Shin
authors.forename: Sukwoo
authors.initials: S
authors.lastname: Choi
mesh_terms: D000679:Amygdala / Q000033:anatomy & histology* / Q000502:physiology*; D000818:Animals; D001921:Brain / Q000378:metabolism; D004566:Electrodes; D004594:Electrophysiology / Q000379:methods; D004705:Endocytosis; D005239:Fear; D008297:Male; D010455:Peptides / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000378:metabolism; D013569:Synapses / Q000378:metabolism; D013574:Synaptosomes / Q000378:metabolism
chemical_list: D010455:Peptides; D018091:Receptors, AMPA; C104722:glutamate receptor ionotropic, AMPA 2