AMPA receptors control fear extinction through an Arc-dependent mechanism

Trent, Simon

doi:10.1101/lm.045013.117

AMPA receptors control fear extinction through an Arc-dependent mechanism

Trent, Simon

Authors

Simon Trent s.trent@keele.ac.uk

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.

Journal Article Type	Article
Acceptance Date	Apr 21, 2017
Online Publication Date	Jul 17, 2017
Publication Date	2017-08
Journal	Learning & Memory
Print ISSN	1072-0502
Publisher	Cold Spring Harbor Laboratory Press
Peer Reviewed	Peer Reviewed
Volume	24
Issue	8
Pages	375 - 380
DOI	https://doi.org/10.1101/lm.045013.117
Keywords	AMPA receptors, Arc-dependent mechanism
Publisher URL	http://learnmem.cshlp.org/content/24/8/375