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- Title
Neurological dysfunctions in mice expressing different levels of the Q/R site-unedited AMPAR subunit GluR-B.
- Authors
Feldmeyer, D; Kask, K; Brusa, R; Kornau, H C; Kolhekar, R; Rozov, A; Burnashev, N; Jensen, V; Hvalby, O; Sprengel, R; Seeburg, P H
- 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.
- Publication
Nature neuroscience, 1999, Vol 2, Issue 1, p57
- ISSN
1097-6256
- Publication type
Journal Article
- DOI
10.1038/4561