Chronic alcohol remodels prefrontal neurons and disrupts NMDAR-mediated fear extinction encoding
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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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Dendritic hypotrophy in mPFC neurons has been linked to stress and alcohol-related deficits in fear extinction.
“Reciprocal connections between the BLA and mPFC are important for fear extinction, fear discrimination, and other processes requiring the resolution of conflicting information (47–50), and dendritic hypotrophy in mPFC neurons has been linked to stress and alcohol-related deficits in fear extinction (51,52).”
From Chronic Stress Remodels Synapses in an Amygdala Circuit-Specific Manner (2019) · cites this paper as [52]
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- Authors
- Holmes, A., Fitzgerald, P. J., MacPherson, K. P., DeBrouse, L., Colacicco, G., Flynn, S. M., Masneuf, S., Pleil, K. E., Li, C., Marcinkiewcz, C. A., Kash, T. L., Gunduz-Cinar, O., & Camp, M.
- Affiliations
- National Institutes of Health (US)
- University of North Carolina at Chapel Hill (US)
- Corresponding author
- Holmes, Andrew
- ORCID
- Venue
- Nature Neuroscience
- Published
- 2012-09-02
- Volume
- 15
- Issue
- 10
- Pages
- 1359-1361
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- PMC
- PMC3471649
- OpenAlex
- W2079005883
- Cited by
- 218
- References
- 23
- Citations by year
- 2026: 4 · 2025: 10 · 2024: 12 · 2023: 12 · 2022: 6 · 2021: 9 · 2020: 19 · 2019: 22 · 2018: 20 · 2017: 13 · 2016: 17 · 2015: 33 · 2014: 25 · 2013: 13 · 2012: 3
- FWCI
- 12.13
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion)
- UNC Libraries
- Funders
- U.S. Department of Defense
- National Alliance for Research on Schizophrenia and Depression
- Center for Alcohol Studies
- National Institutes of Health (AA017668)
- Center for Neuroscience and Regenerative Medicine
- National Institute on Alcohol Abuse and Alcoholism (AA019454, K99AA017668, AA017668, F32AA021043, R00AA017668, AA020911, AA021043, ZIAAA000411, R01AA019454, U01AA020911)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- chronic intermittent ethanol, alcoholism, fear extinction, fear conditioning, medial prefrontal cortex, infralimbic cortex, NMDA receptor, GluN1, post-traumatic stress disorder, neuronal excitability
- MeSH terms
- Action Potentials, Ethanol, Animals, Dendrites, Extinction, Psychological, Fear, Neurons, Down-Regulation, Receptors, N-Methyl-D-Aspartate, Prefrontal Cortex, Mice
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