title: Striatal D1 and D2 signaling differentially predict learning from positive and negative outcomes.
abstract: The extent to which we learn from positive and negative outcomes of decisions is modulated by the neurotransmitter dopamine. Dopamine neurons burst fire in response to unexpected rewards and pause following negative outcomes. This dual signaling mechanism is hypothesized to drive both approach and avoidance behavior. Here we test a prediction deriving from a computational reinforcement learning model, in which approach is mediated via activation of the direct cortico-striatal pathway due to striatal D1 receptor stimulation, while avoidance occurs via disinhibition of indirect pathway striatal neurons secondary to a reduction of D2 receptor stimulation. Using positron emission tomography with two separate radioligands, we demonstrate that individual differences in human approach and avoidance learning are predicted by variability in striatal D1 and D2 receptor binding, respectively. Moreover, transient dopamine precursor depletion improved learning from negative outcomes. These findings support a bidirectional modulatory role for striatal dopamine in reward and avoidance learning via segregated D1 and D2 cortico-striatal pathways.
authors.affiliation: Montreal Neurological Institute, McGill University, 3801 University Street, Montreal, Quebec H3A 2B4, Canada; Department of Psychiatry, McGill University, 1033 Pine Avenue West, Montreal, Quebec H3A 1A1, Canada.
authors.forename: Sylvia M L
authors.initials: SM
authors.lastname: Cox
authors.affiliation: Department of Cognitive, Linguistic & Psychological Sciences, Brown Institute for Brain Science, Brown University, 190 Thayer Street, Providence, RI 02912-1821, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Frank
authors.affiliation: Montreal Neurological Institute, McGill University, 3801 University Street, Montreal, Quebec H3A 2B4, Canada; Department of Psychiatry, McGill University, 1033 Pine Avenue West, Montreal, Quebec H3A 1A1, Canada.
authors.forename: Kevin
authors.initials: K
authors.lastname: Larcher
authors.affiliation: Montreal Neurological Institute, McGill University, 3801 University Street, Montreal, Quebec H3A 2B4, Canada.
authors.forename: Lesley K
authors.initials: LK
authors.lastname: Fellows
authors.affiliation: Montreal Neurological Institute, McGill University, 3801 University Street, Montreal, Quebec H3A 2B4, Canada.
authors.forename: Crystal A
authors.initials: CA
authors.lastname: Clark
authors.affiliation: Department of Psychiatry, McGill University, 1033 Pine Avenue West, Montreal, Quebec H3A 1A1, Canada.
authors.forename: Marco
authors.initials: M
authors.lastname: Leyton
authors.affiliation: Montreal Neurological Institute, McGill University, 3801 University Street, Montreal, Quebec H3A 2B4, Canada. Electronic address: alain.dagher@mcgill.ca.
authors.forename: Alain
authors.initials: A
authors.lastname: Dagher
mesh_terms: D000328:Adult; D001362:Avoidance Learning / Q000502:physiology*; D002755:Choice Behavior / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D017072:Neostriatum / Q000000981:diagnostic imaging / Q000378:metabolism*; D049268:Positron-Emission Tomography; D017447:Receptors, Dopamine D1 / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D012054:Reinforcement, Psychology; D055815:Young Adult
chemical_list: D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2
keywords: Dopamine; Learning; Positron emission tomography; Reinforcement; Striatum