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Nat Neurosci. 2013 Aug;16(8):1101-10. doi: 10.1038/nn.3457. Epub 2013 Jul 7.

GluN2B in corticostriatal circuits governs choice learning and choice shifting.

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1
Laboratory of Behavioral and Genomic Neuroscience, National Institute on Alcoholism and Alcohol Abuse (NIAAA), US National Institutes of Health (NIH), Bethesda, Maryland, USA.

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.

PMID:
23831965
PMCID:
PMC3725191
DOI:
10.1038/nn.3457
[Indexed for MEDLINE]
Free PMC Article
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