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Related Experiment Video

Updated: Jul 8, 2026

Extinction Training During the Reconsolidation Window Prevents Recovery of Fear

Extinction Training During the Reconsolidation Window Prevents Recovery of Fear

Published on: August 24, 2012

Amygdala depotentiation and fear extinction.

Jeongyeon Kim¹, Sukwon Lee, Kyungjoon Park

¹School of Biological Sciences, College of Natural Sciences, Seoul National University, Seoul 151-742, Korea.

Proceedings of the National Academy of Sciences of the United States of America

|January 1, 2008

Summary

Fear extinction involves depotentiation, a process that reverses synaptic potentiation in the lateral amygdala (LA). This study shows AMPA receptor (AMPAR) removal at LA synapses underlies fear memory extinction.

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Area of Science:

Neuroscience
Molecular Biology
Behavioral Psychology

Background:

Auditory fear memory is maintained by synaptic potentiation in the lateral amygdala (LA).
Depotentiation, the reversal of synaptic potentiation, is hypothesized to be a mechanism for fear extinction.
A direct link between depotentiation and fear extinction has not been established.

Purpose of the Study:

To investigate the role of depotentiation in fear extinction.
To determine if depotentiation reverses fear conditioning-induced synaptic potentiation in the LA.
To elucidate the molecular mechanisms underlying fear extinction in the LA.

Main Methods:

Ex vivo and in vivo electrophysiology in rats with consolidated fear memory.
Synaptosomal preparations to assess surface AMPA receptor (AMPAR) expression.
Pharmacological manipulation using a GluR2-derived peptide to block AMPAR endocytosis.

Main Results:

A novel form of depotentiation reversed fear conditioning-induced potentiation at thalamic input synapses onto the LA (T-LA synapses) ex vivo.
Fear extinction returned enhanced T-LA synaptic efficacy to baseline and occluded depotentiation.
Fear extinction reversed conditioning-induced enhancement of surface AMPAR expression in the LA, suggesting AMPAR removal underlies extinction.

Conclusions:

Depotentiation weakens potentiated synaptic inputs onto the LA during fear extinction.
AMPA receptor (AMPAR) removal at excitatory synapses in the LA is a key cellular mechanism for fear extinction.
Targeting AMPAR endocytosis may offer therapeutic strategies for fear-related disorders.