Amygdala depotentiation and fear extinction.
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.
Kim
Jeongyeon
J
School of Biological Sciences, College of Natural Sciences, Seoul National University, Seoul 151-742, Korea.
Lee
Sukwon
S
Park
Kyungjoon
K
Hong
Ingie
I
Song
Beomjong
B
Son
Gihoon
G
Park
Heewoo
H
Kim
Woon Ryoung
WR
Park
Eunjin
E
Choe
Han Kyung
HK
Kim
Hyun
H
Lee
Changjoong
C
Sun
Woong
W
Kim
Kyungjin
K
Shin
Ki Soon
KS
Choi
Sukwoo
S
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
D010455:Peptides; D018091:Receptors, AMPA; C104722:glutamate receptor ionotropic, AMPA 2