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GluN2B in corticostriatal circuits governs choice learning and choice shifting.

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.

Pubmed ID: 23831965


  • Brigman JL
  • Daut RA
  • Wright T
  • Gunduz-Cinar O
  • Graybeal C
  • Davis MI
  • Jiang Z
  • Saksida LM
  • Jinde S
  • Pease M
  • Bussey TJ
  • Lovinger DM
  • Nakazawa K
  • Holmes A


Nature neuroscience

Publication Data

August 26, 2013

Associated Grants

  • Agency: Wellcome Trust, Id: 089703
  • Agency: Intramural NIH HHS, Id: ZIA AA000411-09
  • Agency: Wellcome Trust, Id:

Mesh Terms

  • Adaptation, Psychological
  • Animals
  • Anticipation, Psychological
  • Choice Behavior
  • Conditioning, Operant
  • Corpus Striatum
  • Decision Making
  • Discrimination Learning
  • Excitatory Amino Acid Antagonists
  • Gene Deletion
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Nerve Net
  • Nerve Tissue Proteins
  • Neuronal Plasticity
  • Patch-Clamp Techniques
  • Pattern Recognition, Visual
  • Phenols
  • Piperidines
  • Prefrontal Cortex
  • Receptors, N-Methyl-D-Aspartate
  • Reward