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Chronic alcohol remodels prefrontal neurons and disrupts NMDAR-mediated fear extinction encoding


Holmes, Andrew; Fitzgerald, Paul J; MacPherson, Kathryn P; DeBrouse, Lauren; Colacicco, Giovanni; Flynn, Shaun M; Masneuf, Sophie; Pleil, Kristen E; Li, Chia; Marcinkiewcz, Catherine A; Kash, Thomas L; Gunduz-Cinar, Ozge; Camp, Marguerite (2012). Chronic alcohol remodels prefrontal neurons and disrupts NMDAR-mediated fear extinction encoding. Nature Neuroscience, 15(10):1359-1361.

Abstract

Alcoholism is frequently co-morbid with post-traumatic stress disorder, but it is unclear how alcohol affects the neural circuits mediating recovery from trauma. We found that chronic intermittent ethanol (CIE) impaired fear extinction and remodeled the dendritic arbor of medial prefrontal cortical (mPFC) neurons in mice. CIE impaired extinction encoding by infralimbic mPFC neurons in vivo and functionally downregulated burst-mediating NMDA GluN1 receptors. These findings suggest that alcohol may increase risk for trauma-related anxiety disorders by disrupting mPFC-mediated extinction of fear.

Abstract

Alcoholism is frequently co-morbid with post-traumatic stress disorder, but it is unclear how alcohol affects the neural circuits mediating recovery from trauma. We found that chronic intermittent ethanol (CIE) impaired fear extinction and remodeled the dendritic arbor of medial prefrontal cortical (mPFC) neurons in mice. CIE impaired extinction encoding by infralimbic mPFC neurons in vivo and functionally downregulated burst-mediating NMDA GluN1 receptors. These findings suggest that alcohol may increase risk for trauma-related anxiety disorders by disrupting mPFC-mediated extinction of fear.

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67 citations in Web of Science®
70 citations in Scopus®
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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Anatomy
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:2012
Deposited On:07 Feb 2013 09:57
Last Modified:05 Apr 2016 16:30
Publisher:Nature Publishing Group
ISSN:1097-6256
Publisher DOI:https://doi.org/10.1038/nn.3204
PubMed ID:22941108

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