Restraint stress induces low-frequency NAc LFP oscillations and impairs reward anticipation Thus, stress elicits VTA-NAc GABAergic activity that induces VTA GABA mediated blunted reward-seeking.
Finally, we find that stress disrupts VTA GABA, but not DA, neural encoding of reward anticipation. By contrast, mimicking this signature of stress by stimulating NAc-projecting VTA GABA neurons at 4 Hz reproduces both oscillations and blunted reward-seeking. Inhibiting VTA GABA neurons disrupts stress-induced NAc oscillations and rescues 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. We recorded simultaneous neural activity across limbic brain areas as mice underwent stress and discovered a stress-induced 4 Hz oscillation in the nucleus accumbens (NAc) that predicts the degree of subsequent blunted reward-seeking. Stressful experiences precipitate depression and disrupt reward-seeking, but it remains unclear how stress causes anhedonia. Decreased pleasure-seeking (anhedonia) forms a core symptom of depression.
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