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

• DOI: 10.1038/s41467-021-23906-2
• Publication Date: 2021-06-10T10:04:33Z
• Authors: Daniel C. Lowes; Linda A. Chamberlin; Lisa N. Kretsge; Emma S. Holt; Atheir I. Abbas; Alan J. Park; Lyubov Yusufova; Zachary H. Bretton; Ayesha Firdous; Armen G. Enikolopov; Joshua A. Gordon; Alexander Z. Harris
• Keywords: Brain stimulation reward

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 discovered stress-induced 4 Hz oscillation in the nucleus accumbens (NAc) that predicts degree subsequent blunted reward-seeking. Surprisingly, while previous studies on reward-seeking focused dopamine (DA) transmission from ventral tegmental area (VTA) to NAc, we found VTA GABA, not DA, neurons mediate Inhibiting GABA disrupts NAc oscillations rescues By contrast, mimicking this signature by stimulating NAc-projecting at reproduces both Finally, find encoding reward anticipation. Thus, elicits VTA-NAc GABAergic induces mediated