title: Neurological dysfunctions in mice expressing different levels of the Q/R site-unedited AMPAR subunit GluR-B.
abstract: 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.
authors: Department of Molecular Neurobiology, Max-Planck-Institute for Medical Research, Heidelberg, Germany.
authors: D
authors: D
authors: Feldmeyer
authors: K
authors: K
authors: Kask
authors: R
authors: R
authors: Brusa
authors: H C
authors: HC
authors: Kornau
authors: R
authors: R
authors: Kolhekar
authors: A
authors: A
authors: Rozov
authors: N
authors: N
authors: Burnashev
authors: V
authors: V
authors: Jensen
authors: O
authors: O
authors: Hvalby
authors: R
authors: R
authors: Sprengel
authors: P H
authors: PH
authors: Seeburg
mesh_terms: D000483:Alleles; D000818:Animals; D001921:Brain / Q000473:pathology; D002118:Calcium / Q000378:metabolism / Q000502:physiology; D004553:Electric Conductivity; D015870:Gene Expression / Q000502:physiology*; D006624:Hippocampus / Q000503:physiopathology; D017774:Long-Term Potentiation / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic / Q000235:genetics; D009422:Nervous System Diseases / Q000235:genetics*; D009434:Neural Pathways / Q000503:physiopathology; D010641:Phenotype; D018091:Receptors, AMPA / Q000502:physiology; D017470:Receptors, Glutamate / Q000235:genetics*
chemical_list: D018091:Receptors, AMPA; D017470:Receptors, Glutamate; C115953:glutamate receptor type B; D002118:Calcium