Circuit specificity in the inhibitory architecture of the VTA regulates cocaine-induced behavior

Nicholas J. Edwards, Hugo A. Tejeda, Marco Pignatelli, Shiliang Zhang, Ross A. McDevitt, Jocelyn Wu, Caroline E. Bass, Bernhard Bettler, Marisela Morales, Antonello Bonci

Research output: Contribution to journalArticlepeer-review

70 Scopus citations

Abstract

Afferent inputs to the ventral tegmental area (VTA) control reward-related behaviors through regulation of dopamine neuron activity. The nucleus accumbens (NAc) provides one of the most prominent projections to the VTA; however, recent studies have provided conflicting evidence regarding the function of these inhibitory inputs. Using optogenetics, cell-specific ablation, whole cell patch-clamp and immuno-electron microscopy, we found that NAc inputs synapsed directly onto dopamine neurons, preferentially activating GABA B receptors. GABAergic inputs from the NAc and local VTA GABA neurons were differentially modulated and activated separate receptor populations in dopamine neurons. Genetic deletion of GABA B receptors from dopamine neurons in adult mice did not affect general or morphine-induced locomotor activity, but markedly increased cocaine-induced locomotion. Collectively, our findings demonstrate notable selectivity in the inhibitory architecture of the VTA and suggest that long-range GABAergic inputs to dopamine neurons fundamentally regulate behavioral responses to cocaine.

Original languageEnglish
Pages (from-to)438-448
Number of pages11
JournalNature neuroscience
Volume20
Issue number3
DOIs
StatePublished - Feb 23 2017

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