Negative Reward Signals from the Lateral Habenula to Dopamine Neurons Are Mediated by Rostromedial Tegmental Nucleus in Primates
Open accessAbstract
Lateral habenula (LHb) neurons signal negative “reward-prediction errors” and inhibit midbrain dopamine (DA) neurons. Yet LHb neurons are largely glutamatergic, indicating that this inhibition may occur through an intermediate structure. Recent studies in rats have suggested a candidate for this role, the GABAergic rostromedial tegmental nucleus (RMTg), but this neural pathway has not yet been tested directly. We now show using electrophysiology and anatomic tracing that (1) the monkey has an inhibitory structure similar to the rat RMTg; (2) RMTg neurons receive excitatory input from the LHb, exhibit negative reward-prediction errors, and send axonal projections near DA soma; and (3) stimulating this structure inhibits DA neurons. Surprisingly, some RMTg neurons responded to reward cues earlier than the LHb, and carry “state-value” signals not found in DA neurons. Thus, our data suggest that the RMTg translates LHb reward-prediction errors (negative) into DA reward-prediction errors (positive), while transmitting additional motivational signals to non-DA networks.
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RMTg activity increases with aversive stimuli and decreases with reward stimuli, showing inversely correlated signaling patterns.
“Activity in the RMTg increases upon exposure to aversive stimuli and decreases upon exposure to reward stimuli, representing inversely correlated signaling patterns (Hong et al. 2011).”
From Nicotine Withdrawal (2015) · cites this paper as Hong et al. 2011
The Results (‘Reward-related properties of primate RMTg neurons’; page not provided) report that reward-negative neurons increased activity when an expected reward was absent and decreased activity when an unexpected reward occurred. The paper also reports reward-positive neurons with the opposite pattern. It supports inverse responses to reward versus non-reward in a subset of RMTg neurons, but does not establish the claimed response to aversive stimuli generally. (LLM, conf=0.88)
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- Authors
- Hong, S., Jhou, T. C., Smith, M., Saleem, K. S., & Hikosaka, O.
- Affiliations
- National Institutes of Health (US)
- Medical University of South Carolina (US)
- National Eye Institute (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2011-08-10
- Volume
- 31
- Issue
- 32
- Pages
- 11457-11471
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC3315151
- OpenAlex
- W2083338953
- Cited by
- 390
- References
- 29
- Citations by year
- 2026: 23 · 2025: 11 · 2024: 28 · 2023: 12 · 2022: 19 · 2021: 27 · 2020: 18 · 2019: 28 · 2018: 25 · 2017: 21 · 2016: 36 · 2015: 39 · 2014: 38 · 2013: 33 · 2012: 21
- FWCI
- 13.37
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (Z99 EY999999)
- National Eye Institute (ZIAEY000415)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- lateral habenula, rostromedial tegmental nucleus, dopaminergic neurons, GABAergic interneurons, reward processing, primate brain, glutamatergic inhibition
- MeSH terms
- Animals, Dopamine, Macaca mulatta, Male, Neural Inhibition, Neurons, Photic Stimulation, Psychomotor Performance, Reward, Signal Transduction, Habenula, Pedunculopontine Tegmental Nucleus
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