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

Cited 32 time in Web of Science Cited 34 time in Scopus
Authors

Lowes, Daniel C.; Chamberlin, Linda A.; Kretsge, Lisa N.; Holt, Emma S.; Abbas, Atheir, I; Park, Alan J.; Yusufova, Lyubov; Bretton, Zachary H.; Firdous, Ayesha; Enikolopov, Armen G.; Gordon, Joshua A.; Harris, Alexander Z.

Issue Date
2021-06
Publisher
NATURE RESEARCH
Citation
NATURE COMMUNICATIONS, Vol.12 No.1
Abstract
Decreased 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.
ISSN
2041-1723
URI
https://hdl.handle.net/10371/203353
DOI
https://doi.org/10.1038/s41467-021-23906-2
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Research Area Computational decoding, Electrophysiology, Neuroscience

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