Journal article
Chronic intermittent ethanol exposure dysregulates a GABAergic microcircuit in the bed nucleus of the stria terminalis
Neuropharmacology, Vol.168, pp.107759-107759
05/15/2020
DOI: 10.1016/j.neuropharm.2019.107759
PMID: 31494142
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 (CRFnon−VTA/LH neurons) was increased. Withdrawal from CIE also increased excitability of non-CRF BNST neurons that project to both LH and VTA (BNSTnon−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 BNSTnon−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’.
•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.
Details
- Title: Subtitle
- Chronic intermittent ethanol exposure dysregulates a GABAergic microcircuit in the bed nucleus of the stria terminalis
- Creators
- Dipanwita Pati - Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, Thurston Bowles Building 104 Manning Drive, Chapel Hill, NC, 27599, USACatherine A Marcinkiewcz - Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, Thurston Bowles Building 104 Manning Drive, Chapel Hill, NC, 27599, USAJeffrey F DiBerto - Department of Pharmacology, University of North Carolina School of Medicine, Chapel Hill, NC, 2751, USAElizabeth S Cogan - Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, Thurston Bowles Building 104 Manning Drive, Chapel Hill, NC, 27599, USAZoe A McElligott - Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, Thurston Bowles Building 104 Manning Drive, Chapel Hill, NC, 27599, USAThomas L Kash - Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, Thurston Bowles Building 104 Manning Drive, Chapel Hill, NC, 27599, USA
- Resource Type
- Journal article
- Publication Details
- Neuropharmacology, Vol.168, pp.107759-107759
- DOI
- 10.1016/j.neuropharm.2019.107759
- PMID
- 31494142
- NLM abbreviation
- Neuropharmacology
- ISSN
- 0028-3908
- eISSN
- 1873-7064
- Publisher
- Elsevier Ltd
- Grant note
- DOI: 10.13039/100000027, name: National Institute on Alcohol Abuse and Alcoholism, award: U01 AA020911, P60 AA011605, U24 AA025475, K01AA023555, K99A024215, R01 AA019454
- Language
- English
- Date published
- 05/15/2020
- Academic Unit
- Iowa Neuroscience Institute; Neuroscience and Pharmacology
- Record Identifier
- 9984070375002771
Metrics
15 Record Views