Increased NMDA current and spine density in mice lacking the NMDA receptor subunit NR3A

Saumya Das, Yasnory F. Sasaki, Thomas Rothe, Louis S. Premkumar, Mari Takasu, James E. Crandall, Pieter Dikkes, David A. Conner, Posina V. Rayudu, Wing Cheung, H.-S. Vincent Chen, Stuart A. Lipton () and Nobuki Nakanishi ()
Additional contact information
Saumya Das: Harvard Medical School
Yasnory F. Sasaki: Harvard Medical School
Thomas Rothe: Cerebrovascular and NeuroScience Research Institute, Neurosurgical Service, Brigham and Women's Hospital
Louis S. Premkumar: State University of New York
Mari Takasu: Harvard Medical School
James E. Crandall: The Shriver Center for Mental Retardation
Pieter Dikkes: Children's Hospital
David A. Conner: Harvard Medical School
Posina V. Rayudu: Cerebrovascular and NeuroScience Research Institute, Neurosurgical Service, Brigham and Women's Hospital
Wing Cheung: Cerebrovascular and NeuroScience Research Institute, Neurosurgical Service, Brigham and Women's Hospital
H.-S. Vincent Chen: Cerebrovascular and NeuroScience Research Institute, Neurosurgical Service, Brigham and Women's Hospital
Stuart A. Lipton: Cerebrovascular and NeuroScience Research Institute, Neurosurgical Service, Brigham and Women's Hospital
Nobuki Nakanishi: Harvard Medical School

Nature, 1998, vol. 393, issue 6683, 377-381

Abstract: Abstract The NMDA (N -methyl-D-aspartate) subclass of glutamate receptor1 is essential for the synaptic plasticity thought to underlie learning and memory2,3,4 and for synaptic refinement during development5,6. It is currently believed that the NMDA receptor (NMDAR) is a heteromultimeric channel comprising the ubiquitous NR1 subunit and at least one regionally localized NR2 subunit7,8,9,10,11. Here we report the characterization of a regulatory NMDAR subunit, NR3A (formerly termed NMDAR-L or χ-1), which is expressed primarily during brain development12,13. NR3Aco-immunoprecipitates with receptor subunits NR1 and NR2 in cerebrocortical extracts. In single-channel recordings from Xenopus oocytes, addition of NR3A to NR1 and NR2 leads to the appearance of a smaller unitary conductance. Genetic knockout of NR3A in mice results in enhanced NMDA responses and increased dendritic spines in early postnatal cerebrocortical neurons. These data suggest that NR3A is involved in the development of synaptic elements by modulating NMDAR activity.

Date: 1998
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DOI: 10.1038/30748

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