Multiphasic Temporal Dynamics in Responses of Midbrain Dopamine Neurons to Appetitive and Aversive Stimuli
Open accessAbstract
The transient response of dopamine neurons has been described as reward prediction error (RPE), with activation or suppression by events that are better or worse than expected, respectively. However, at least a minority of neurons are activated by aversive or high-intensity stimuli, casting doubt on the generality of RPE in describing the dopamine signal. To overcome limitations of previous studies, we studied neuronal responses to a wider variety of high-intensity and aversive stimuli, and we quantified and controlled aversiveness through a choice task in which macaques sacrificed juice to avoid aversive stimuli. Whereas most previous work has portrayed the RPE as a single impulse or “phase,” here we demonstrate its multiphasic temporal dynamics. Aversive or high-intensity stimuli evoked a triphasic sequence of activation-suppression-activation extending over a period of 40–700 ms. The initial activation at short latencies (40–120 ms) reflected sensory intensity. The influence of motivational value became dominant between 150 and 250 ms, with activation in the case of appetitive stimuli, and suppression in the case of aversive and neutral stimuli. The previously unreported late activation appeared to be a modest “rebound” after strong suppression. Similarly, strong activation by reward was often followed by suppression. We suggest that these “rebounds” may result from overcompensation by homeostatic mechanisms in some cells. Our results are consistent with a realistic RPE, which evolves over time through a dynamic balance of excitation and inhibition.
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Recent reports that distinguished between different stimulus components of punishers suggest that the physical impact of punishers is the major determinant for dopamine activations, and the psychophysically assessed aversive nature of the punishers did not explain the recorded dopamine activations.
“However, recent reports that distinguished between different stimulus components of punishers suggest that the physical impact of punishers is the major determinant for dopamine activations, and the psychophysically assessed aversive nature of the punishers did not explain the recorded dopamine activations25–27.”
From Dopamine reward prediction-error signalling: A two-component response (2016) · cites this paper as [25]
The initial dopamine activation is enhanced by stimuli of sufficient physical intensity in a graded manner, irrespective of their positive or negative value associations.
“Stimuli of sufficient physical intensity elicit the initial dopamine activation in a graded manner (FIG. 3a), irrespective of their positive or negative value associations25.”
From Dopamine reward prediction-error signalling: A two-component response (2016) · cites this paper as [25]
The improbability of truly aversive dopamine activations makes the interpretation that the dopamine prediction-error response mediates attention derived from motivational salience unlikely.
“However, the improbability of truly aversive dopamine activations25 make this interpretation unlikely.”
From Dopamine reward prediction-error signalling: A two-component response (2016) · cites this paper as [25]
Because aversive responses may primarily concern the initial response component, their regional distributions might be explained by varying sensitivities to stimulus intensity, reward context and reward generalization.
“However, because aversive responses may primarily concern the initial response component25, it is possible that their regional distributions might be explained by varying sensitivities to stimulus intensity, reward context and reward generalization (FIG. 3).”
From Dopamine reward prediction-error signalling: A two-component response (2016) · cites this paper as [25]
Phasic dopamine activations by aversive stimuli constitute the initial, unselective dopamine response component driven by physical impact, possibly boosted by reward context and reward generalization, rather than reflecting a straightforward aversive response.
“The phasic dopamine activations by aversive stimuli seem to constitute the initial, unselective dopamine response component driven by physical impact25, and possibly boosted by reward context and reward generalization19, rather than reflecting a straightforward aversive response”
From Dopamine reward prediction-error signalling: A two-component response (2016) · cites this paper as [25]
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- Authors
- Fiorillo, C. D., Song, M. R., & Yun, S. R.
- Affiliations
- Korea Advanced Institute of Science and Technology (KR)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2013-03-13
- Volume
- 33
- Issue
- 11
- Pages
- 4710-4725
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC3873404
- OpenAlex
- W1963806202
- Cited by
- 98
- References
- 45
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 3 · 2023: 3 · 2022: 6 · 2021: 3 · 2020: 6 · 2019: 8 · 2018: 7 · 2017: 10 · 2016: 12 · 2015: 14 · 2014: 11 · 2013: 6
- FWCI
- 7.03
- 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
- Howard Hughes Medical Institute
- National Research Foundation
- National Research Foundation of Korea
- Ministry of Education, Science and Technology (R32-2008-000-10218-0)
- National Eye Institute (R01EY005603)
- 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 › Neural dynamics and brain function
- Keywords
- dopaminergic neurons, reward prediction error, aversive stimuli, midbrain, macaque, sensory intensity, motivational value, excitation-inhibition balance, homeostatic compensation, appetitive stimuli, temporal dynamics
- MeSH terms
- Acoustic Stimulation, Action Potentials, Animals, Appetitive Behavior, Avoidance Learning, Choice Behavior, Conditioning, Classical, Female, Judgment, Macaca mulatta, Male, Mesencephalon, Motivation, Neural Inhibition, Reaction Time, Regression Analysis, Reinforcement, Psychology, Time Factors, Nonlinear Dynamics, Dopaminergic Neurons
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