1. GluN2B in corticostriatal circuits governs choice learning and choice shifting.
- Author
-
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, and Holmes A
- Subjects
- Adaptation, Psychological physiology, Animals, Anticipation, Psychological physiology, Decision Making physiology, Excitatory Amino Acid Antagonists pharmacology, Gene Deletion, Male, Mice, Mice, Inbred C57BL, Mice, Transgenic, Nerve Tissue Proteins antagonists & inhibitors, Nerve Tissue Proteins deficiency, Nerve Tissue Proteins genetics, Neuronal Plasticity, Patch-Clamp Techniques, Phenols pharmacology, Piperidines pharmacology, Receptors, N-Methyl-D-Aspartate antagonists & inhibitors, Receptors, N-Methyl-D-Aspartate deficiency, Receptors, N-Methyl-D-Aspartate genetics, Reward, Choice Behavior physiology, Conditioning, Operant physiology, Corpus Striatum physiology, Discrimination Learning physiology, Nerve Net physiology, Nerve Tissue Proteins physiology, Pattern Recognition, Visual physiology, Prefrontal Cortex physiology, Receptors, N-Methyl-D-Aspartate physiology
- 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.
- Published
- 2013
- Full Text
- View/download PDF