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

Andrew Holmes; Paul J Fitzgerald; Kathryn P MacPherson; Lauren DeBrouse; Giovanni Colacicco; Shaun M Flynn; Sophie Masneuf; Kristen E Pleil; Chia Li; Catherine A Marcinkiewcz; Thomas L Kash; Ozge Gunduz-Cinar; Marguerite Camp

doi:10.1038/nn.3204

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

Journal article

Peer reviewed

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

Andrew Holmes, Paul J Fitzgerald, Kathryn P MacPherson, Lauren DeBrouse, Giovanni Colacicco, Shaun M Flynn, Sophie Masneuf, Kristen E Pleil, Chia Li, Catherine A Marcinkiewcz, …

Nature neuroscience, Vol.15(10), pp.1359-1361

10/2012

DOI: 10.1038/nn.3204

PMCID: PMC3471649

PMID: 22941108

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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.

Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors

Ethanol - administration & dosage

Extinction, Psychological - drug effects

Dendrites - ultrastructure

Down-Regulation - drug effects

Fear - physiology

Receptors, N-Methyl-D-Aspartate - physiology

Action Potentials - physiology

Down-Regulation - physiology

Ethanol - pharmacology

Animals

Prefrontal Cortex - drug effects

Neurons - physiology

Mice

Prefrontal Cortex - physiology

Extinction, Psychological - physiology

Details

Title: Subtitle: Chronic alcohol remodels prefrontal neurons and disrupts NMDAR-mediated fear extinction encoding
Creators: Andrew Holmes - Laboratory of Behavioral and Genomic Neuroscience, National Institute on Alcohol Abuse and Alcoholism, US National Institutes of Health, Bethesda, Maryland, USA. andrew.holmes@nih.gov
Paul J Fitzgerald
Kathryn P MacPherson
Lauren DeBrouse
Giovanni Colacicco
Shaun M Flynn
Sophie Masneuf
Kristen E Pleil
Chia Li
Catherine A Marcinkiewcz
Thomas L Kash
Ozge Gunduz-Cinar
Marguerite Camp
Resource Type: Journal article
Publication Details: Nature neuroscience, Vol.15(10), pp.1359-1361
Publisher: United States
DOI: 10.1038/nn.3204
PMID: 22941108
PMCID: PMC3471649
ISSN: 1097-6256
eISSN: 1546-1726
Grant note: AA019454 / NIAAA NIH HHS AA021043 / NIAAA NIH HHS U01 AA020911 / NIAAA NIH HHS F32 AA021043 / NIAAA NIH HHS AA020911 / NIAAA NIH HHS R01 AA019454 / NIAAA NIH HHS ZIA AA000411-08 / Intramural NIH HHS R00 AA017668 / NIAAA NIH HHS K99 AA017668 / NIAAA NIH HHS AA017668 / NIAAA NIH HHS
Language: English
Date published: 10/2012
Academic Unit: Iowa Neuroscience Institute; Neuroscience and Pharmacology
Record Identifier: 9984040233402771

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