Severely impaired learning and altered neuronal morphology in mice lacking NMDA receptors in medium spiny neurons
Beutler, Lisa R. (University of Washington. Department of Genome Sciences)
Eldred, Kiara C. (Howard Hughes Medical Institute (Estats Units d'Amèrica))
Quintana Romero, Albert (University of Washington. Department of Biochemistry)
Keene, C. Dirk (University of Washington. Department of Pathology)
Rose, Shannon E. (University of Washington. Department of Pathology)
Postupna, Nadia (University of Washington. Department of Pathology)
Montine, Thomas J. (University of Washington. Department of Pathology)
Palmiter, Richard D. (University of Washington. Department of Genome Sciences)

Data:	2011
Resum:	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.
Nota:	This work was supported by the Howard Hughes Medical Institute and grants from the Udall Center (NS062684), NIGMS T32 GM07735, and the ARCS Foundation. A.Q. is a recipient of a MCINN postdoctoral mobility program fellowship. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Aprenentatge motor ; Receptors neurals ; Neuroplasticitat ; Memòria ; Rates (Animals de laboratori) ; Experiments
Publicat a:	PloS one, Vol. 6 Num. 11 (November 2011) , p. e28168, ISSN 1932-6203

DOI: 10.1371/journal.pone.0028168
PMID: 22132236

9 p, 1.4 MB

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