title: Chronic alcohol remodels prefrontal neurons and disrupts NMDAR-mediated fear extinction encoding.
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.
authors.affiliation: 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
authors.forename: Andrew
authors.initials: A
authors.lastname: Holmes
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Fitzgerald
authors.forename: Kathryn P
authors.initials: KP
authors.lastname: MacPherson
authors.forename: Lauren
authors.initials: L
authors.lastname: DeBrouse
authors.forename: Giovanni
authors.initials: G
authors.lastname: Colacicco
authors.forename: Shaun M
authors.initials: SM
authors.lastname: Flynn
authors.forename: Sophie
authors.initials: S
authors.lastname: Masneuf
authors.forename: Kristen E
authors.initials: KE
authors.lastname: Pleil
authors.forename: Chia
authors.initials: C
authors.lastname: Li
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Marcinkiewcz
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Kash
authors.forename: Ozge
authors.initials: O
authors.lastname: Gunduz-Cinar
authors.forename: Marguerite
authors.initials: M
authors.lastname: Camp
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D003712:Dendrites / Q000648:ultrastructure*; D015536:Down-Regulation / Q000187:drug effects* / Q000502:physiology; D000431:Ethanol / Q000008:administration & dosage / Q000494:pharmacology*; D005108:Extinction, Psychological / Q000187:drug effects* / Q000502:physiology; D005239:Fear / Q000502:physiology; D051379:Mice; D009474:Neurons / Q000502:physiology; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000502:physiology*
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate; D000431:Ethanol