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Ventral tegmental area GABA neurons mediate stress-induced blunted reward-seeking in mice

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dc.contributor.authorLowes, Daniel C.-
dc.contributor.authorChamberlin, Linda A.-
dc.contributor.authorKretsge, Lisa N.-
dc.contributor.authorHolt, Emma S.-
dc.contributor.authorAbbas, Atheir, I-
dc.contributor.authorPark, Alan J.-
dc.contributor.authorYusufova, Lyubov-
dc.contributor.authorBretton, Zachary H.-
dc.contributor.authorFirdous, Ayesha-
dc.contributor.authorEnikolopov, Armen G.-
dc.contributor.authorGordon, Joshua A.-
dc.contributor.authorHarris, Alexander Z.-
dc.date.accessioned2024-05-20T00:39:30Z-
dc.date.available2024-05-20T00:39:30Z-
dc.date.created2024-05-17-
dc.date.issued2021-06-
dc.identifier.citationNATURE COMMUNICATIONS, Vol.12 No.1-
dc.identifier.issn2041-1723-
dc.identifier.urihttps://hdl.handle.net/10371/203353-
dc.description.abstractDecreased pleasure-seeking (anhedonia) forms a core symptom of depression. Stressful experiences precipitate depression and disrupt reward-seeking, but it remains unclear how stress causes anhedonia. We recorded simultaneous neural activity across limbic brain areas as mice underwent stress and discovered a stress-induced 4Hz oscillation in the nucleus accumbens (NAc) that predicts the degree of subsequent blunted reward-seeking. Surprisingly, while previous studies on blunted reward-seeking focused on dopamine (DA) transmission from the ventral tegmental area (VTA) to the NAc, we found that VTA GABA, but not DA, neurons mediate stress-induced blunted reward-seeking. Inhibiting VTA GABA neurons disrupts stress-induced NAc oscillations and rescues reward-seeking. By contrast, mimicking this signature of stress by stimulating NAc-projecting VTA GABA neurons at 4Hz reproduces both oscillations and blunted reward-seeking. Finally, we find that stress disrupts VTA GABA, but not DA, neural encoding of reward anticipation. Thus, stress elicits VTA-NAc GABAergic activity that induces VTA GABA mediated blunted reward-seeking. Acute stress transiently disrupts reward-seeking behaviour and repeated stress exposure produces lasting anhedonia-like behaviour in rodents. Here, the authors show that stress triggers GABAergic activity in the ventral tegmental area which blunts reward-seeking behaviour in mice.-
dc.language영어-
dc.publisherNATURE RESEARCH-
dc.titleVentral tegmental area GABA neurons mediate stress-induced blunted reward-seeking in mice-
dc.typeArticle-
dc.identifier.doi10.1038/s41467-021-23906-2-
dc.citation.journaltitleNATURE COMMUNICATIONS-
dc.identifier.wosid000663747800029-
dc.identifier.scopusid2-s2.0-85107545470-
dc.citation.number1-
dc.citation.volume12-
dc.description.isOpenAccessY-
dc.contributor.affiliatedAuthorPark, Alan J.-
dc.type.docTypeArticle-
dc.description.journalClass1-
dc.subject.keywordPlusCHOLINERGIC INTERNEURONS-
dc.subject.keywordPlusNUCLEUS-ACCUMBENS-
dc.subject.keywordPlusTHETA OSCILLATIONS-
dc.subject.keywordPlusDOPAMINE NEURONS-
dc.subject.keywordPlusVTA-
dc.subject.keywordPlusACTIVATION-
dc.subject.keywordPlusDEPRESSION-
dc.subject.keywordPlusANHEDONIA-
dc.subject.keywordPlusCIRCUITRY-
dc.subject.keywordPlusSALIENCE-
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Research Area Computational decoding, Electrophysiology, Neuroscience

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