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Volume 16, Number 16, Issue of August 15, 1996 pp. 5014-5025
Copyright ©1996 Society for NeuroscienceModification of NMDA Receptor Channels and Synaptic Transmission by Targeted Disruption of the NR2C Gene
Received March 22, 1996; revised May 29, 1996; accepted June 3, 1996.
Alexander K. Ebralidze1, David J. Rossi2, Susumu Tonegawa1, and N. Traverse Slater2 1 Center for Learning and Memory, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139-4307, and 2 Department of Physiology, Northwestern University Medical School, Chicago, Illinois 60611-3008
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.
Key words: cerebellum; granule cells; NMDA receptors; synaptic transmission; patch-clamp; gene knockout
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