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AMPA receptors control fear extinction through an Arc-dependent mechanism.

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.

SUBMITTER: Trent S

PROVIDER: S-EPMC5516687 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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AMPA receptors control fear extinction through an Arc-dependent mechanism.

Trent Simon S Barnes Philip P Hall Jeremy J Thomas Kerrie L KL

Learning & memory (Cold Spring Harbor, N.Y.) 20170717 8

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 ...[more]

PMID: 28716957

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