Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.05.28.121905v1?rss=1 Authors: Lowes, D. C., Chamberlin, L. A., Kretsge, L. N., Holt, E. S., Abbas, A. I., Park, A. J., Yusufova, L., Bretton, Z. H., Firdous, A., Gordon, J. A., Harris, A. Z. Abstract: Stressful experiences frequently precede depressive episodes. Depression results in anhedonia, or disrupted reward-seeking, in most patients. In humans and rodents stress can disrupt reward-seeking, providing a potential mechanism by which stress can precipitate depression. Yet despite decades investigating how stress modulates dopamine neuron transmission between the ventral tegmental area (VTA) and nucleus accumbens (NAc), the underpinnings of the stress-anhedonia transition remain elusive. Here we show that during restraint stress, VTA GABA neurons drive low frequency NAc LFP oscillations, rhythmically modulating NAc firing rates. The strength of these stress-induced NAc oscillations predict the degree of impaired reward-seeking upon release from restraint. Inhibiting VTA GABA neurons disrupts stress-induced NAc oscillations and reverses the effect of stress on reward-seeking. By contrast, mimicking these oscillations with rhythmic VTA GABA stimulation in the absence of stress blunts subsequent reward-seeking. These experiments demonstrate that VTA GABA inputs to the NAc are both necessary and sufficient for stress-induced decreases in reward seeking behavior, elucidating a key circuit-level mechanism underlying stress-induced anhedonia. Copy rights belong to original authors. Visit the link for more info