Journal
NATURE
Volume 491, Issue 7423, Pages 212-+Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nature11527
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Funding
- National Institutes of Health [NIH NS069375]
- Simons Foundation
- DARPA REPAIR program
- Wiegers Family Fund
- German Academy of Sciences Leopoldina
- Davis Foundation Postdoctoral Fellowship in Eating Disorders Research
- JPB Foundation
- NIMH
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Ventral tegmental area (VTA) dopamine neurons have important roles in adaptive and pathological brain functions related to reward and motivation. However, it is unknown whether subpopulations of VTA dopamine neurons participate in distinct circuits that encode different motivational signatures, and whether inputs to the VTA differentially modulate such circuits. Here we show that, because of differences in synaptic connectivity, activation of inputs to the VTA from the laterodorsal tegmentum and the lateral habenula elicit reward and aversion in mice, respectively. Laterodorsal tegmentum neurons preferentially synapse on dopamine neurons projecting to the nucleus accumbens lateral shell, whereas lateral habenula neurons synapse primarily on dopamine neurons projecting to the medial prefrontal cortex as well as on GABAergic (gamma-aminobutyric-acid-containing) neurons in the rostromedial tegmental nucleus. These results establish that distinct VTA circuits generate reward and aversion, and thereby provide a new framework for understanding the circuit basis of adaptive and pathological motivated behaviours.
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