title: Akt1 deficiency modulates reward learning and reward prediction error in mice.
abstract: In contemporary reinforcement learning models, reward prediction error (RPE), the difference between the expected and actual reward, is thought to guide action value learning through the firing activity of dopaminergic neurons. Given the importance of dopamine in reward learning and the involvement of Akt1 in dopamine-dependent behaviors, the aim of this study was to investigate whether Akt1 deficiency modulates reward learning and the magnitude of RPE using Akt1 mutant mice as a model. In comparison to wild-type littermate controls, the expression of Akt1 proteins in mouse brains occurred in a gene-dosage-dependent manner and Akt1 heterozygous (HET) mice exhibited impaired striatal Akt1 activity under methamphetamine challenge. No genotypic difference was found in the basal levels of dopamine and its metabolites. In a series of reward-related learning tasks, HET mice displayed a relatively efficient method of updating reward information from the environment during the acquisition phase of the two natural reward tasks and in the reverse section of the dynamic foraging T-maze but not in methamphetamine-induced or aversive-related reward learning. The implementation of a standard reinforcement learning model and the Bayesian hierarchical parameter estimation show that HET mice have higher RPE magnitudes and that their action values are updated more rapidly among all three test sections in T-maze. These results indicate that Akt1 deficiency modulates natural reward learning and RPE. This study showed a promising avenue for investigating RPE in mutant mice and provided evidence for the potential link from genetic deficiency, to neurobiological abnormalities, to impairment in higher-order cognitive functioning.
authors.affiliation: Department of Psychology, National Taiwan University, 1 Roosevelt Road Sec. 4, Taipei, Taiwan.
authors.forename: Y-C
authors.initials: YC
authors.lastname: Chen
authors.forename: Y-W
authors.initials: YW
authors.lastname: Chen
authors.forename: Y-F
authors.initials: YF
authors.lastname: Hsu
authors.forename: W-T
authors.initials: WT
authors.lastname: Chang
authors.forename: C K
authors.initials: CK
authors.lastname: Hsiao
authors.forename: M-Y
authors.initials: MY
authors.lastname: Min
authors.forename: W-S
authors.initials: WS
authors.lastname: Lai
mesh_terms: D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D007858:Learning / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008959:Models, Neurological; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics* / Q000378:metabolism; D012201:Reward
chemical_list: D018765:Dopamine Uptake Inhibitors; D000661:Amphetamine; C514862:Akt1 protein, mouse; D051057:Proto-Oncogene Proteins c-akt; D004298:Dopamine