Activity patterns of serotonin neurons underlying cognitive flexibility
Open accessAbstract
Serotonin is implicated in mood and affective disorders. However, growing evidence suggests that a core endogenous role is to promote flexible adaptation to changes in the causal structure of the environment, through behavioral inhibition and enhanced plasticity. We used long-term photometric recordings in mice to study a population of dorsal raphe serotonin neurons, whose activity we could link to normal reversal learning using pharmacogenetics. We found that these neurons are activated by both positive and negative prediction errors, and thus report signals similar to those proposed to promote learning in conditions of uncertainty. Furthermore, by comparing the cue responses of serotonin and dopamine neurons, we found differences in learning rates that could explain the importance of serotonin in inhibiting perseverative responding. Our findings show how the activity patterns of serotonin neurons support a role in cognitive flexibility, and suggest a revised model of dopamine-serotonin opponency with potential clinical implications.
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The authors' results and framework, including how learning from worse-than-expected outcomes is affected, agree with earlier observations and manipulations of serotonin neurons.
“Our findings and conceptual framework, including the effect on learning from worse-than-expected outcomes, are consistent with previous observations and manipulations of serotonin neuron activity.”
From Serotonin neurons modulate learning rate through uncertainty (2022) · cites this paper as [33]
In that Pavlovian reversal task, chemogenetic inhibition of serotonin neurons disrupted adaptation to a cue that had predicted reward before reversal, but not after reversal.
“Chemogenetic inhibition of serotonin neurons in this task impaired behavioral adaptation to a cue that predicted reward prior to the reversal, but not after.”
From Serotonin neurons modulate learning rate through uncertainty (2022) · cites this paper as [33]
Serotonin axon lesions or reversible inactivation of dorsal raphe serotonin neurons impaired behavioral adaptation to changes in action- or stimulus-outcome mappings.
“Serotonin axon lesions37,38 or reversible inactivation of dorsal raphe serotonin neurons33 impaired behavioral adaptation to changes in action- or stimulus-outcome mappings.”
From Serotonin neurons modulate learning rate through uncertainty (2022) · cites this paper as [33]
Prior research demonstrates that serotonin neurons modulate flexible behavior in changing environments.
“Prior research demonstrates that serotonin neurons modulate flexible behavior in changing environments.33,37–42”
From Serotonin neurons modulate learning rate through uncertainty (2022) · cites this paper as [33]
In a Pavlovian reversal task, serotonin neuron population responses to changed cue-outcome mappings diminished as mice adjusted to the new mapping.
“In a Pavlovian reversal task, changes in cue-outcome mappings elicited responses from populations of serotonin neurons that decayed as mice adapted their behavior to the new mapping.33”
From Serotonin neurons modulate learning rate through uncertainty (2022) · cites this paper as [33]
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References 84 · Cited by 239
- Authors
- Matias, S., Lottem, E., Dugué, G. P., & Mainen, Z. F.
- Affiliations
- Centro Champalimaud (PT)
- Champalimaud Research, Champalimaud Centre for the Unknown, Lisbon, Portugal
- Centre National de la Recherche Scientifique (FR)
- Corresponding author
- Mainen, Zachary F
- Venue
- eLife
- Publisher
- eLife Sciences Publications, Ltd
- Published
- 2017-03-21
- Volume
- 6
- ISSN
- 2050-084X (ISSN-L)
- PMC
- PMC5360447
- OpenAlex
- W2434010258
- Cited by
- 239
- References
- 84
- Citations by year
- 2026: 26 · 2025: 22 · 2024: 31 · 2023: 28 · 2022: 23 · 2021: 24 · 2020: 33 · 2019: 16 · 2018: 20 · 2017: 15 · 2016: 1
- FWCI
- 11.37
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- eLife (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT) (submittedVersion, other-oa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Fundação para a Ciência e a Tecnologia (SFRH/BD/43072/2008)
- Human Frontier Science Program (LT00088/011L)
- European Research Council (250334, 671251)
- Champalimaud Foundation
- 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
- serotonergic neurons, dorsal raphe nucleus, cognitive flexibility, reversal learning, prediction error, perseverative responding, learning rate, pharmacogenetics, uncertainty, behavioral inhibition
- MeSH terms
- Animals, Reversal Learning, Mice, Serotonergic Neurons, Dorsal Raphe Nucleus
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