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Input-specific control of reward and aversion in the ventral tegmental area

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Lammel, Stephan, Lim, Byung Kook, Ran, Chen, Huang, Kee Wui, Betley, Michael J., Tye, Kay M., Deisseroth, Karl, Malenka, Robert C.·2012·Nature

DOI 10.1038/nature11527PMC PMC3493743

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Abstract

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 (γ-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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Authors: Lammel, S., Lim, B. K., Ran, C., Huang, K. W., Betley, M. J., Tye, K. M., Deisseroth, K., & Malenka, R. C.
Affiliations: Stanford Medicine (US)
Massachusetts Institute of Technology (US)
Stanford University (US)
Corresponding author: Malenka, Robert C.
ORCID: Lammel, Stephan
Lim, Byung Kook
Huang, Kee Wui
Tye, Kay M.
Deisseroth, Karl
Malenka, Robert C.
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 2012-10-14
Volume: 491
Issue: 7423
Pages: 212-217
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/nature11527
PMC: PMC3493743
OpenAlex: W2140986639
Cited by: 1,300
References: 43
Citations by year: 2026: 55 · 2025: 69 · 2024: 78 · 2023: 73 · 2022: 84 · 2021: 101 · 2020: 91 · 2019: 105 · 2018: 118 · 2017: 105 · 2016: 113 · 2015: 101 · 2014: 115 · 2013: 82 · 2012: 6
FWCI: 40.06
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springer.com/tdm (tdm)
Locations: Nature (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
RePEc: Research Papers in Economics (submittedVersion)
eScholarship (California Digital Library) (submittedVersion)
PMC
Funders: National Institute of Mental Health (P50MH086403)
National Institute of Diabetes and Digestive and Kidney Diseases (DP2DK102256)
National Institute of Neurological Disorders and Stroke (NS069375, P30NS069375)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
Keywords: ventral tegmental area, dopaminergic neurons, reward, aversion, laterodorsal tegmentum, lateral habenula, synaptic connectivity, medial prefrontal cortex, rostromedial tegmental nucleus, GABAergic neurons
MeSH terms: Animals, Avoidance Learning, Axons, Dopamine, Male, Mice, Inbred C57BL, Models, Neurological, Neural Pathways, Receptors, Dopamine, Reward, Synapses, Ventral Tegmental Area, Dopamine Antagonists, Habenula, Mice, Dopaminergic Neurons, GABAergic Neurons

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Input-specific control of reward and aversion in the ventral tegmental area

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