Neuron-type-specific signals for reward and punishment in the ventral tegmental area
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Dopamine has a central role in motivation and reward. Dopaminergic neurons in the ventral tegmental area (VTA) signal the discrepancy between expected and actual rewards (that is, reward prediction error), but how they compute such signals is unknown. We recorded the activity of VTA neurons while mice associated different odour cues with appetitive and aversive outcomes. We found three types of neuron based on responses to odours and outcomes: approximately half of the neurons (type I, 52%) showed phasic excitation after reward-predicting odours and rewards in a manner consistent with reward prediction error coding; the other half of neurons showed persistent activity during the delay between odour and outcome that was modulated positively (type II, 31%) or negatively (type III, 18%) by the value of outcomes. Whereas the activity of type I neurons was sensitive to actual outcomes (that is, when the reward was delivered as expected compared to when it was unexpectedly omitted), the activity of type II and type III neurons was determined predominantly by reward-predicting odours. We 'tagged' dopaminergic and GABAergic neurons with the light-sensitive protein channelrhodopsin-2 and identified them based on their responses to optical stimulation while recording. All identified dopaminergic neurons were of type I and all GABAergic neurons were of type II. These results show that VTA GABAergic neurons signal expected reward, a key variable for dopaminergic neurons to calculate reward prediction error.
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Associative learning is driven by the activity of dopamine neurons in the midbrain, where spiking activity resembles the reward prediction error (RPE) signal in temporal difference (TD) learning.
“one successful theoretical model posits that associative learning is driven by the activity of dopamine neurons in the midbrain, where spiking activity resembles the reward prediction error (RPE) signal in an RL algorithm called temporal difference (TD) learning [1][2][3][4].”
From Emergence of belief-like representations through reinforcement learning (2023) · cites this paper as [3]
Animal research indicates that dopaminergic neurons are strongly excited by acute stress and aversive stimuli during adulthood.
“Animal research indicates that dopaminergic neurons are strongly excited by acute stress and aversive stimuli during adulthood (Brischoux et al., 2009; Cohen et al., 2012; Wenzel et al., 2015; Zweifel et al., 2011).”
From The effects of psychosocial stress on dopaminergic function and the acute stress response (2019) · cites this paper as Cohen et al., 2012
Ventral tegmental area dopaminergic neurons also respond to aversive events.
“they also respond to aversive events [21, 22]”
From The molecular and cellular mechanisms of depression: a focus on reward circuitry (2019) · cites this paper as [22]
These slow changes fail to occur with more-controlled arm, mouth and eye movements in a considerable range of studies.
“these changes fail to occur with more-controlled arm, mouth and eye movements in a considerable range of studies2,5,9,13,151,152,154”
From Dopamine reward prediction-error signalling: A two-component response (2016) · cites this paper as [154]
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- Authors
- Cohen, J. Y., Haesler, S., Vong, L., Lowell, B. B., & Uchida, N.
- Affiliations
- Harvard University (US)
- Beth Israel Deaconess Medical Center (US)
- Corresponding author
- Uchida, Naoshige
- Venue
- Nature
- Published
- 2012-01-18
- Volume
- 482
- Issue
- 7383
- Pages
- 85-88
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC3271183
- OpenAlex
- W2022561563
- Cited by
- 1,318
- References
- 29
- Citations by year
- 2026: 52 · 2025: 115 · 2024: 90 · 2023: 78 · 2022: 99 · 2021: 116 · 2020: 113 · 2019: 106 · 2018: 100 · 2017: 83 · 2016: 88 · 2015: 102 · 2014: 69 · 2013: 63 · 2012: 43
- FWCI
- 36.51
- 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)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institute of Mental Health (R01MH095953)
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK057521, R01DK075632, R01DK089044, P30DK046200, F32DK078478)
- 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
- ventral tegmental area, dopaminergic neurons, GABAergic neurons, reward prediction error, reward anticipation, aversive stimuli, dopamine, channelrhodopsin-2
- MeSH terms
- Channelrhodopsins, Animals, Cues, Dopamine, gamma-Aminobutyric Acid, Male, Mice, Inbred C57BL, Odorants, Punishment, Reward, Ventral Tegmental Area, Principal Component Analysis, Mice, Dopaminergic Neurons, GABAergic Neurons
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