title: GluN2B in corticostriatal circuits governs choice learning and choice shifting.
abstract: A choice that reliably produces a preferred outcome can be automated to liberate cognitive resources for other tasks. Should an outcome become less desirable, behavior must adapt in parallel or it becomes perseverative. Corticostriatal systems are known to mediate choice learning and flexibility, but the molecular mechanisms of these processes are not well understood. We integrated mouse behavioral, immunocytochemical, in vivo electrophysiological, genetic and pharmacological approaches to study choice. We found that the dorsal striatum (DS) was increasingly activated with choice learning, whereas reversal of learned choice engaged prefrontal regions. In vivo, DS neurons showed activity associated with reward anticipation and receipt that emerged with learning and relearning. Corticostriatal or striatal deletion of Grin2b (encoding the NMDA-type glutamate receptor subunit GluN2B) or DS-restricted GluN2B antagonism impaired choice learning, whereas cortical Grin2b deletion or OFC GluN2B antagonism impaired shifting. Our convergent data demonstrate how corticostriatal GluN2B circuits govern the ability to learn and shift choice behavior.
authors.affiliation: Laboratory of Behavioral and Genomic Neuroscience, National Institute on Alcoholism and Alcohol Abuse (NIAAA), US National Institutes of Health (NIH), Bethesda, Maryland, USA.
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Brigman
authors.forename: Rachel A
authors.initials: RA
authors.lastname: Daut
authors.forename: Tara
authors.initials: T
authors.lastname: Wright
authors.forename: Ozge
authors.initials: O
authors.lastname: Gunduz-Cinar
authors.forename: Carolyn
authors.initials: C
authors.lastname: Graybeal
authors.forename: Margaret I
authors.initials: MI
authors.lastname: Davis
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Jiang
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Saksida
authors.forename: Seiichiro
authors.initials: S
authors.lastname: Jinde
authors.forename: Matthew
authors.initials: M
authors.lastname: Pease
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Bussey
authors.forename: David M
authors.initials: DM
authors.lastname: Lovinger
authors.forename: Kazu
authors.initials: K
authors.lastname: Nakazawa
authors.forename: Andrew
authors.initials: A
authors.lastname: Holmes
mesh_terms: D000223:Adaptation, Psychological / Q000502:physiology; D000818:Animals; D059031:Anticipation, Psychological / Q000502:physiology; D002755:Choice Behavior / Q000502:physiology*; D003216:Conditioning, Operant / Q000502:physiology*; D003342:Corpus Striatum / Q000502:physiology*; D003657:Decision Making / Q000502:physiology; D004193:Discrimination Learning / Q000502:physiology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D017353:Gene Deletion; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009415:Nerve Net / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D009473:Neuronal Plasticity; D018408:Patch-Clamp Techniques; D010364:Pattern Recognition, Visual / Q000502:physiology*; D010636:Phenols / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D017397:Prefrontal Cortex / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D012201:Reward
chemical_list: D018691:Excitatory Amino Acid Antagonists; C121001:NR2B NMDA receptor; D009419:Nerve Tissue Proteins; D010636:Phenols; D010880:Piperidines; D016194:Receptors, N-Methyl-D-Aspartate; C109643:Ro 25-6981