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

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

  1. catseye
    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

    Nature Neuroscience
    September 2, 2012
    Advance Online Publication

    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.