Neurological dysfunctions in mice expressing different levels of the Q/R site-unedited AMPAR subunit GluR-B

Nat Neurosci. 1999 Jan;2(1):57-64. doi: 10.1038/4561.


We generated mouse mutants with targeted AMPA receptor (AMPAR) GluR-B subunit alleles, functionally expressed at different levels and deficient in Q/R-site editing. All mutant lines had increased AMPAR calcium permeabilities in pyramidal neurons, and one showed elevated macroscopic conductances of these channels. The AMPAR-mediated calcium influx induced NMDA-receptor-independent long-term potentiation (LTP) in hippocampal pyramidal cell connections. Calcium-triggered neuronal death was not observed, but mutants had mild to severe neurological dysfunctions, including epilepsy and deficits in dendritic architecture. The seizure-prone phenotype correlated with an increase in the macroscopic conductance, as independently revealed by the effect of a transgene for a Q/R-site-altered GluR-B subunit. Thus, changes in GluR-B gene expression and Q/R site editing can affect critical architectural and functional aspects of excitatory principal neurons.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Animals
  • Brain / pathology
  • Calcium / metabolism
  • Calcium / physiology
  • Electric Conductivity
  • Gene Expression / physiology*
  • Hippocampus / physiopathology
  • Long-Term Potentiation / physiology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic / genetics
  • Nervous System Diseases / genetics*
  • Neural Pathways / physiopathology
  • Phenotype
  • Receptors, AMPA / physiology
  • Receptors, Glutamate / genetics*


  • Receptors, AMPA
  • Receptors, Glutamate
  • glutamate receptor type B
  • Calcium