Input-specific control of reward and aversion in the ventral tegmental area
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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 (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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Habenula stimulation elicits inhibitory electrophysiological dopamine responses through an intermediate reticular nucleus, rather than the excitatory responses required for a postulated aversive dopamine influence on place preferences.
“In support of the latter result, habenula stimulation elicits inhibitory electrophysiological dopamine responses139–141 through an intermediate reticular nucleus138, rather than the excitatory responses required for a postulated aversive dopamine influence on place preferences137.”
From Dopamine reward prediction-error signalling: A two-component response (2016) · cites this paper as [137]
This subpopulation of DA neurons projects to the medial prefrontal cortex and the medial shell of the nucleus accumbens.
“Anatomically, this subpopulation of DA neurons projects to the medial prefrontal cortex and the medial shell of the nucleus accumbens (Lammel et al., 2011; Lammel et al., 2012).”
From Dopamine regulates aversive contextual learning and associated in vivo synaptic plasticity in the Hippocampus (2016) · cites this paper as Lammel et al., 2012
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“…targeted the lateral PBP, which is a more lateral subdivision of the VTA where dopamine neurons predominantly project to the lateral shell of the NAc (Lammel et al., 2008; Lammel et al., 2011) and play a primary role in reward and motivated behavior (Lammel et al., 2011; Lammel et al., 2012).”
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Self-citation
- 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.
- Venue
- Nature
- Published
- 2012-10-14
- Volume
- 491
- Issue
- 7423
- Pages
- 212-217
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- 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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