Modification of NMDA Receptor Channels and Synaptic Transmission by Targeted Disruption of the NR2C Gene

A novel strain of mutant mouse has been generated with a deletion of the gene encoding the NR2C subunit of the NMDA receptor, which is primarily expressed in cerebellar granule cells. Patch-clamp recordings from granule cells in thin cerebellar slices were used to assess the consequences of the gene...

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Bibliographic Details
Published in:The Journal of neuroscience 1996-08, Vol.16 (16), p.5014-5025
Main Authors: Ebralidze, Alexander K, Rossi, David J, Tonegawa, Susumu, Slater, N. Traverse
Format: Article
Language:English
Subjects:
Animals
Cerebellum - cytology
Cerebellum - metabolism
Electric Conductivity
Gene Targeting
Genes
Ion Channel Gating
Ion Channels - physiology
Mice
Mice, Inbred C57BL
Mice, Knockout
Nerve Fibers - physiology
Rats
Rats, Sprague-Dawley
Receptors, N-Methyl-D-Aspartate - genetics
Receptors, N-Methyl-D-Aspartate - metabolism
Synapses - physiology
Synaptic Transmission
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Summary:A novel strain of mutant mouse has been generated with a deletion of the gene encoding the NR2C subunit of the NMDA receptor, which is primarily expressed in cerebellar granule cells. Patch-clamp recordings from granule cells in thin cerebellar slices were used to assess the consequences of the gene deletion. In granule cells of wild-type animals, a wide range of single-channel conductances were observed (19-60 pS). The disruption of the NR2C gene results in the disappearance of low-conductance NMDA receptor channels ( < 37 pS) normally expressed in granule cells during developmental maturation. The NMDA receptor-mediated synaptic current is markedly potentiated in amplitude, but abbreviated in duration (with no net difference in total charge), and the non-NMDA component of the synaptic current was reduced. We conclude that the NR2C subunit contributes to functional heteromeric NMDA receptor-subunit assemblies at the mossy fiber synapse and extrasynaptic sites during maturation, and the conductance level exhibited by a given receptor macromolecule may reflect the stochiometry of subunit composition.
ISSN:0270-6474
1529-2401
DOI:10.1523/jneurosci.16-16-05014.1996