Chronic intermittent ethanol exposure dysregulates a GABAergic microcircuit in the bed nucleus of the stria terminalis. (15th May 2020)

• Record Type: Journal Article
• Authors: Pati, Dipanwita; Marcinkiewcz, Catherine A.; DiBerto, Jeffrey F.; Cogan, Elizabeth S.; McElligott, Zoe A.; Kash, Thomas L.
• Is Part Of: Neuropharmacology. Volume 168(2020)
• Publication Date: 2020-05-15
• Subjects: Ethanol -- BNST -- VTA -- LH -- CRF -- GABA; Neuropsychopharmacology -- Periodicals; Autonomic Agents -- Periodicals; Neuropsychopharmacologie -- Périodiques; Neuropsychopharmacology; Periodicals; Electronic journals; 615.78
• DOI: 10.1016/j.neuropharm.2019.107759
• Languages: English
• ISSNs: 0028-3908

Abstract

Abstract: Neuroadaptations in brain regions that regulate emotional and reward-seeking behaviors have been suggested to contribute to pathological behaviors associated with alcohol-use disorder. One such region is the bed nucleus of the stria terminalis (BNST), which has been linked to both alcohol consumption and alcohol withdrawal-induced anxiety and depression. Recently, we identified a GABAergic microcircuit in the BNST that regulates anxiety-like behavior. In the present study, we examined how chronic alcohol exposure alters this BNST GABAergic microcircuit in mice. We selectively targeted neurons expressing corticotropin releasing factor (CRF) using a CRF-reporter mouse line and combined retrograde labeling to identify BNST projections to the ventral tegmental area (VTA) and lateral hypothalamus (LH). Following 72 h of withdrawal from four weekly cycles of chronic intermittent ethanol (CIE) vapor exposure, the excitability of a sub-population of putative local CRF neurons that did not project to either VTA or LH (CRF non−VTA/LH neurons) was increased. Withdrawal from CIE also increased excitability of non-CRF BNST neurons that project to both LH and VTA (BNST non−CRF-proj neurons). Furthermore, both populations of neurons had a reduction in spontaneous EPSC amplitude while frequency was unaltered. Withdrawal from chronic alcohol was accompanied by a significant increase in spontaneous IPSC frequency selectively in the BNST non−CRF-proj neurons. Together, these data suggest that withdrawal from chronic ethanol dysregulates local CRF-GABAergic microcircuit to inhibit anxiolytic outputs of the BNST which may contribute to enhanced anxiety during alcohol withdrawal and drive alcohol-seeking behavior. This article is part of the special issue on 'Neuropeptides'. Highlights: CIE increased the excitability of a subset of BNST-CRF neurons. CIE increased GABAergic signaling on non-CRF BNST neurons projecting to VTA and LH. These data show withdrawal-induced dysregulation of BNST microcircuit.