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Updated: Feb 26, 2026

Ex Vivo Optogenetic Dissection of Fear Circuits in Brain Slices
Published on: April 5, 2016
AMPA receptors control fear extinction through an Arc-dependent mechanism
Simon Trent1, Philip Barnes2, Jeremy Hall1,3
1Neuroscience and Mental Health Research Institute, Cardiff University, Haydn Ellis Building, Cardiff CF24 4HQ, United Kingdom.
Abstract:
Activity-regulated cytoskeleton-associated protein (Arc) supports fear memory through synaptic plasticity events requiring actin cytoskeleton rearrangements. We have previously shown that reducing hippocampal Arc levels through antisense knockdown leads to the premature extinction of contextual fear. Here we show that the AMPA receptor antagonist CNQX elevates hippocampal Arc levels during extinction and blocks extinction that can be rescued by reducing Arc. Increasing Arc levels with CNQX also overcomes the actin-destabilizing properties of cytochalasin D and promotes extinction. Therefore, extinction is dependent on AMPA-mediated reductions of Arc via a mechanism consistent with a role for Arc in stabilizing the actin cytoskeleton to constrain extinction.
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