Nicotinic receptors in the ventral tegmental area promote uncertainty-seeking
Abstract
Cholinergic neurotransmission affects decision-making, notably through the modulation of perceptual processing in the cortex. In addition, acetylcholine acts on value-based decisions through as yet unknown mechanisms. We found that nicotinic acetylcholine receptors (nAChRs) expressed in the ventral tegmental area (VTA) are involved in the translation of expected uncertainty into motivational value. We developed a multi-armed bandit task for mice with three locations, each associated with a different reward probability. We found that mice lacking the nAChR β2 subunit showed less uncertainty-seeking than their wild-type counterparts. Using model-based analysis, we found that reward uncertainty motivated wild-type mice, but not mice lacking the nAChR β2 subunit. Selective re-expression of the β2 subunit in the VTA was sufficient to restore spontaneous bursting activity in dopamine neurons and uncertainty-seeking. Our results reveal an unanticipated role for subcortical nAChRs in motivation induced by expected uncertainty and provide a parsimonious account for a wealth of behaviors related to nAChRs in the VTA expressing the β2 subunit.
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ACh provides complex regulation of reward and motivation behaviors through its actions on dopamine circuitry.
“ACh provides a complex regulation of reward and motivation behaviors through its actions on dopamine (DA) circuitry [68–72].”
From Adolescent nicotine exposure and persistent neurocircuitry changes: unveiling lifelong psychiatric risks (2025) · cites this paper as [71]
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- Authors
- Naudé, J., Tolu, S., Dongelmans, M., Torquet, N., Valverde, S., Rodriguez, G., Pons, S., Maskos, U., Mourot, A., Marti, F., & Faure, P.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- ORCID
- Venue
- Nature Neuroscience
- Published
- 2016-01-18
- Volume
- 19
- Issue
- 3
- Pages
- 471-478
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- OpenAlex
- W2258027427
- Cited by
- 61
- References
- 56
- Citations by year
- 2026: 4 · 2025: 7 · 2024: 3 · 2023: 6 · 2022: 8 · 2021: 2 · 2020: 8 · 2019: 7 · 2018: 9 · 2017: 5 · 2016: 2
- FWCI
- 3.98
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Funders
- Agence Nationale de la Recherche (ANR-11-LABX-0035, ANR-14-CE13-0019)
- Centre National de la Recherche Scientifique
- Université Pierre et Marie Curie
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Keywords
- nicotinic acetylcholine receptors, ventral tegmental area, decision making under uncertainty, acetylcholine, reward probability, motivation
- MeSH terms
- Animals, Mice, Transgenic, Motivation, Receptors, Nicotinic, Reward, Self Stimulation, Ventral Tegmental Area, Mice, Knockout, Uncertainty, Dopaminergic Neurons
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