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Brief Communication
Impaired discrimination learning in mice lacking the NMDA receptor NR2A subunit

Jonathan L. Brigman^1,5, Michael Feyder¹, Lisa M. Saksida^2,3, Timothy J. Bussey^2,3, Masayoshi Mishina⁴, and Andrew Holmes¹

¹ Section on Behavioral Science and Genetics, Laboratory for Integrative Neuroscience, National Institute on Alcoholism and Alcohol Abuse, National Institutes of Health, Rockville, Maryland 20852, USA; ² Department of Experimental Psychology, University of Cambridge, Cambridge CB2 3EB, United Kingdom; ³ The Medical Research Council and Wellcome Trust Behavioral and Clinical Neuroscience Institute, Cambridge CB2 3EB, United Kingdom; ⁴ Department of Molecular Neurobiology and Pharmacology, Graduate School of Medicine, University of Tokyo, Tokyo 113-0033, Japan

N-Methyl-D-aspartate receptors (NMDARs) mediate certain forms of synaptic plasticity and learning. We used a touchscreen system to assess NR2A subunit knockout mice (KO) for (1) pairwise visual discrimination and reversal learning and (2) acquisition and extinction of an instrumental response requiring no pairwise discrimination. NR2A KO mice exhibited significantly retarded discrimination learning. Performance on reversal was impaired in NR2A KO mice during the learning phase of the task; with no evidence of heightened perseverative responses. Acquisition and extinction of an instrumental behavior requiring no pairwise discrimination was normal in NR2A KO mice. The present findings demonstrate a significant and selective deficit in discrimination learning following loss of NR2A.

⁵ Corresponding author.

E-mail brigmanj{at}mail.nih.gov; fax (301) 480-1952.

Article is online at http://www.learnmem.org/cgi/doi/10.1101/lm.777308

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