Chronic intermittent ethanol exposure dysregulates a GABAergic microcircuit in the bed nucleus of the stria terminalis
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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'.
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- Authors
- Pati, D., Marcinkiewcz, C. A., DiBerto, J. F., Cogan, E. S., McElligott, Z. A., & Kash, T. L.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- Corresponding author
- Kash, Thomas L.
- Venue
- Neuropharmacology
- Publisher
- Elsevier BV
- Published
- 2020-05
- Volume
- 168
- Pages
- 107759
- ISSN
- 0028-3908 (ISSN-L)
- PMC
- PMC7056508
- OpenAlex
- W2971817407
- Cited by
- 59
- References
- 62
- Citations by year
- 2026: 4 · 2025: 7 · 2024: 9 · 2023: 8 · 2022: 8 · 2021: 12 · 2020: 10 · 2019: 1
- FWCI
- 3.70
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Neuropharmacology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
- UNC Libraries
- Funders
- National Institute on Alcohol Abuse and Alcoholism (U01 AA020911, P60 AA011605, U24 AA025475, K01AA023555, K99A024215, R01 AA019454)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- chronic intermittent ethanol, alcohol withdrawal, bed nucleus of the stria terminalis, corticotropin-releasing factor, CRF neurons, neuronal excitability, spontaneous inhibitory postsynaptic currents, spontaneous excitatory postsynaptic currents, ventral tegmental area, lateral hypothalamus, anxiety, alcoholism, alcohol seeking
- MeSH terms
- Ethanol, Animals, Male, Mice, Inbred C57BL, Mice, Transgenic, Nerve Net, Organ Culture Techniques, Septal Nuclei, Mice, GABAergic Neurons
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