Modification of NMDA receptor channels and synaptic transmission by targeted disruption of the NR2C gene

Alexander K. Ebralidze, David J. Rossi, Susumu Tonegawa, N. Traverse Slater

Research output: Contribution to journalArticle

112 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)5014-5025
Number of pages12
JournalJournal of Neuroscience
Volume16
Issue number16
DOIs
StatePublished - Aug 15 1996

Keywords

  • NMDA receptors
  • cerebellum
  • gene knockout
  • granule cells
  • patch- clamp
  • synaptic transmission

ASJC Scopus subject areas

  • Neuroscience(all)

Fingerprint Dive into the research topics of 'Modification of NMDA receptor channels and synaptic transmission by targeted disruption of the NR2C gene'. Together they form a unique fingerprint.

  • Cite this