title: 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.
authors.affiliation: Sorbonne Universités, UPMC University Paris 06, Institut de Biologie Paris Seine, UM 119, Paris, France.|CNRS, UMR 8246, Neuroscience Paris Seine, Paris, France.|INSERM, U1130, Neuroscience Paris Seine, Paris, France.
authors.forename: Jérémie
authors.identifier: http://orcid.org/0000-0001-5781-6498
authors.initials: J
authors.lastname: Naudé
authors.affiliation: Sorbonne Universités, UPMC University Paris 06, Institut de Biologie Paris Seine, UM 119, Paris, France.|CNRS, UMR 8246, Neuroscience Paris Seine, Paris, France.|INSERM, U1130, Neuroscience Paris Seine, Paris, France.
authors.forename: Stefania
authors.initials: S
authors.lastname: Tolu
authors.affiliation: Sorbonne Universités, UPMC University Paris 06, Institut de Biologie Paris Seine, UM 119, Paris, France.|CNRS, UMR 8246, Neuroscience Paris Seine, Paris, France.|INSERM, U1130, Neuroscience Paris Seine, Paris, France.
authors.forename: Malou
authors.initials: M
authors.lastname: Dongelmans
authors.affiliation: Sorbonne Universités, UPMC University Paris 06, Institut de Biologie Paris Seine, UM 119, Paris, France.|CNRS, UMR 8246, Neuroscience Paris Seine, Paris, France.|INSERM, U1130, Neuroscience Paris Seine, Paris, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Torquet
authors.affiliation: Sorbonne Universités, UPMC University Paris 06, Institut de Biologie Paris Seine, UM 119, Paris, France.|CNRS, UMR 8246, Neuroscience Paris Seine, Paris, France.|INSERM, U1130, Neuroscience Paris Seine, Paris, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Valverde
authors.affiliation: Sorbonne Universités, UPMC University Paris 06, Institut de Biologie Paris Seine, UM 119, Paris, France.|CNRS, UMR 8246, Neuroscience Paris Seine, Paris, France.|INSERM, U1130, Neuroscience Paris Seine, Paris, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Rodriguez
authors.affiliation: Institut Pasteur, CNRS UMR 3571, Unité NISC, Paris, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Pons
authors.affiliation: Institut Pasteur, CNRS UMR 3571, Unité NISC, Paris, France.
authors.forename: Uwe
authors.initials: U
authors.lastname: Maskos
authors.affiliation: Sorbonne Universités, UPMC University Paris 06, Institut de Biologie Paris Seine, UM 119, Paris, France.|CNRS, UMR 8246, Neuroscience Paris Seine, Paris, France.|INSERM, U1130, Neuroscience Paris Seine, Paris, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Mourot
authors.affiliation: Sorbonne Universités, UPMC University Paris 06, Institut de Biologie Paris Seine, UM 119, Paris, France.|CNRS, UMR 8246, Neuroscience Paris Seine, Paris, France.|INSERM, U1130, Neuroscience Paris Seine, Paris, France.
authors.forename: Fabio
authors.initials: F
authors.lastname: Marti
authors.affiliation: Sorbonne Universités, UPMC University Paris 06, Institut de Biologie Paris Seine, UM 119, Paris, France.|CNRS, UMR 8246, Neuroscience Paris Seine, Paris, France.|INSERM, U1130, Neuroscience Paris Seine, Paris, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Faure
mesh_terms: D000818:Animals; D059290:Dopaminergic Neurons / Q000502:physiology; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009042:Motivation / Q000502:physiology*; D011978:Receptors, Nicotinic / Q000235:genetics / Q000502:physiology*; D012201:Reward; D012653:Self Stimulation / Q000502:physiology; D035501:Uncertainty; D017557:Ventral Tegmental Area / Q000502:physiology*
chemical_list: D011978:Receptors, Nicotinic