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GluN2B in corticostriatal circuits governs choice learning and choice shifting.

Nature neuroscience | 2013

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 RIS Download

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Associated grants

  • Agency: Wellcome Trust, United Kingdom
    Id: 089703
  • Agency: Medical Research Council, United Kingdom
    Id: G0001354
  • Agency: NIAAA NIH HHS, United States
    Id: K22 AA020303
  • Agency: Intramural NIH HHS, United States
    Id: ZIA AA000411-09

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Jackson Laboratory (tool)

RRID:SCR_004633

An independent, nonprofit organization focused on mammalian genetics research to advance human health. Their mission is to discover the genetic basis for preventing, treating, and curing human disease, and to enable research for the global biomedical community. Jackson Laboratory breeds and manages colonies of mice as resources for other research institutions and laboratories, along with providing software and techniques. Jackson Lab also conducts genetic research and provides educational material for various educational levels.

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C57BL/6J (tool)

RRID:IMSR_JAX:000664

Mus musculus with name C57BL/6J from IMSR.

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Anti-GluN2B/NR2B Glutamate Receptor Antibody (antibody)

RRID:AB_10673405

This monoclonal targets GluN2B/NR2B glutamate receptor

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