Two types of dopamine neuron distinctly convey positive and negative motivational signals
Open accessAbstract
Midbrain dopamine neurons are activated by reward or sensory stimuli predicting reward. These excitatory responses increase as the reward value increases. This response property has led to a hypothesis that dopamine neurons encode value-related signals and are inhibited by aversive events. Here we show that this is true only for a subset of dopamine neurons. We recorded the activity of dopamine neurons in monkeys (Macaca mulatta) during a Pavlovian procedure with appetitive and aversive outcomes (liquid rewards and airpuffs directed at the face, respectively). We found that some dopamine neurons were excited by reward-predicting stimuli and inhibited by airpuff-predicting stimuli, as the value hypothesis predicts. However, a greater number of dopamine neurons were excited by both of these stimuli, inconsistent with the hypothesis. Some dopamine neurons were also excited by both rewards and airpuffs themselves, especially when they were unpredictable. Neurons excited by the airpuff-predicting stimuli were located more dorsolaterally in the substantia nigra pars compacta, whereas neurons inhibited by the stimuli were located more ventromedially, some in the ventral tegmental area. A similar anatomical difference was observed for their responses to actual airpuffs. These findings suggest that different groups of dopamine neurons convey motivational signals in distinct manners.
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High catecholamine release may arise from high tonic firing of norepinephrine neurons and dopamine neurons that respond to aversive events.
“which may arise from high, tonic firing of NE neurons (Aston-Jones et al., 2000; Aston-Jones et al., 1994), and DA neurons that respond to aversive events (Matsumoto and Hikosaka, 2009).”
From Catecholamine influences on prefrontal cortical function: Relevance to treatment of attention deficit/hyperactivity disorder and related disorders (2011) · cites this paper as Matsumoto and Hikosaka, 2009
The striatum and associated DA systems play a prominent role in processing aversive stimuli and processing rewards.
“Moreover, the striatum and associated DA systems play a prominent role in processing aversive stimuli and processing rewards [741,742].”
From Reward circuitry dysfunction in psychiatric and neurodevelopmental disorders and genetic syndromes: animal models and clinical findings (2012) · cites this paper as [742]
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 [21]
Although there are dopaminergic neurons that encode for just positive or negative motivational events, there are more numerous dopaminergic neurons that excite similarly to both threatening and rewarding events.
“Interestingly, although there are dopaminergic neurons that encode for just positive or negative motivational events, there are more numerous dopaminergic neurons that excite similarly to both threatening and rewarding events (Matsumoto & Hikosaka, 2009).”
From Cued for Risk: Evidence for an Incentive Sensitization Framework to Explain the Interplay between Stress and Anxiety, Substance Abuse, and Reward Uncertainty in Disordered Gambling Behavior (2019) · cites this paper as Matsumoto & Hikosaka, 2009
A strong activation in response to the physical impact of an aversive stimulus in particularly sensitive neurons may supersede a depression reflecting the negative value, and this might appear as a categorical difference in aversive and motivational salience coding.
“Thus, a strong activation in response to the physical impact of an aversive stimulus in particularly sensitive neurons may supersede a depression reflecting the negative value, and this might appear as a categorical difference in aversive and motivational salience coding15,23,24,134.”
From Dopamine reward prediction-error signalling: A two-component response (2016) · cites this paper as [24]
Recognition of the two-component structure of phasic dopamine responses may resolve earlier controversies that suggested an attentional rather than rewarding role of the dopamine prediction-error signal.
“Recognition of the two-component structure of phasic dopamine responses may also resolve earlier controversies, which suggested an attentional rather than rewarding role of the dopamine prediction-error signal64,65 on the basis of activations following exposure to physically salient stimuli16,20 and punishers24.”
From Dopamine reward prediction-error signalling: A two-component response (2016) · cites this paper as [24]
Dopamine neurons in medial and lateral, or dorsal and ventral, midbrain positions show graded differences in responses to rewarding and aversive stimuli.
“Dopamine neurons in medial and lateral, or dorsal and ventral, midbrain positions do show graded differences in responses to rewarding and aversive stimuli2,23,24,26,33.”
From Dopamine reward prediction-error signalling: A two-component response (2016) · cites this paper as [24]
In monkeys, a substantial fraction of dopamine neurons in the dorsolateral SN/VTA are responsive to conditioned cues predicting aversive events, whereas those in the more ventromedial portions are inhibited by aversive stimuli.
“In monkeys, a substantial fraction of dopamine neurons in the dorsolateral SN/VTA are responsive to conditioned cues predicting aversive events; in contrast, those in the more ventromedial portions of the SN/VTA are inhibited by aversive stimuli [97]”
From A neoHebbian framework for episodic memory; role of dopamine-dependent late LTP (2011) · cites this paper as [97]
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- Authors
- Matsumoto, M., & Hikosaka, O.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Matsumoto, Masayuki
- Venue
- Nature
- Published
- 2009-05-17
- Volume
- 459
- Issue
- 7248
- Pages
- 837-841
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC2739096
- OpenAlex
- W2144534164
- Cited by
- 1,378
- References
- 42
- Citations by year
- 2026: 44 · 2025: 55 · 2024: 104 · 2023: 71 · 2022: 70 · 2021: 81 · 2020: 79 · 2019: 71 · 2018: 101 · 2017: 75 · 2016: 98 · 2015: 106 · 2014: 94 · 2013: 82 · 2012: 86
- FWCI
- 33.86
- 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)
- Funders
- National Institutes of Health
- National Eye Institute (Z01EY000415)
- 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 › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- dopaminergic neurons, midbrain dopamine, substantia nigra pars compacta, ventral tegmental area, classical conditioning, reward prediction, aversive stimuli, neuronal heterogeneity, reward learning, macaque
- MeSH terms
- Air, Animals, Appetitive Behavior, Conditioning, Classical, Dopamine, Macaca mulatta, Models, Neurological, Motivation, Neurons, Reward
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