Severely impaired learning and altered neuronal morphology in mice lacking NMDA receptors in medium spiny neurons

Lisa R. Beutler, Kiara C. Eldred, Albert Quintana, C. Dirk Keene, Shannon E. Rose, Nadia Postupna, Thomas J. Montine, Richard D. Palmiter

Research output: Contribution to journalArticlepeer-review

26 Scopus citations


The striatum is composed predominantly of medium spiny neurons (MSNs) that integrate excitatory, glutamatergic inputs from the cortex and thalamus, and modulatory dopaminergic inputs from the ventral midbrain to influence behavior. Glutamatergic activation of AMPA, NMDA, and metabotropic receptors on MSNs is important for striatal development and function, but the roles of each of these receptor classes remain incompletely understood. Signaling through NMDA-type glutamate receptors (NMDARs) in the striatum has been implicated in various motor and appetitive learning paradigms. In addition, signaling through NMDARs influences neuronal morphology, which could underlie their role in mediating learned behaviors. To study the role of NMDARs on MSNs in learning and in morphological development, we generated mice lacking the essential NR1 subunit, encoded by the Grin1 gene, selectively in MSNs. Although these knockout mice appear normal and display normal 24-hour locomotion, they have severe deficits in motor learning, operant conditioning and active avoidance. In addition, the MSNs from these knockout mice have smaller cell bodies and decreased dendritic length compared to littermate controls. We conclude that NMDAR signaling in MSNs is critical for normal MSN morphology and many forms of learning.

Original languageEnglish (US)
Article numbere28168
JournalPloS one
Issue number11
StatePublished - Nov 21 2011

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • General
  • Biochemistry, Genetics and Molecular Biology(all)


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