AMPA receptors control fear extinction through an Arc-dependent mechanism

Trent, Simon ORCID: https://orcid.org/0000-0001-9563-4281, Phillip, Barnes, Hall, Jeremy ORCID: https://orcid.org/0000-0003-2737-9009 and Thomas, Kerrie ORCID: https://orcid.org/0000-0003-3355-9583 2017. AMPA receptors control fear extinction through an Arc-dependent mechanism. Learning and Memory 24 , pp. 375-380. 10.1101/lm.045013.117

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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 AMPAR 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 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.

Item Type:	Article
Status:	Published
Schools:	Biosciences Medicine Neuroscience and Mental Health Research Institute (NMHRI) MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Publisher:	Cold Spring Harbor Laboratory Press: 12 month Embargo
ISSN:	1072-0502
Date of First Compliant Deposit:	23 May 2017
Date of Acceptance:	21 April 2017
Last Modified:	05 May 2023 18:57
URI:	https://orca.cardiff.ac.uk/id/eprint/100775

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