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

doi:10.1038/nn.3204

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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. (2012). Chronic alcohol remodels prefrontal neurons and disrupts NMDAR-mediated fear extinction encoding. Nature Neuroscience, 15(10), 1359–1361. https://doi.org/10.1038/nn.3204

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 anxie