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.
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Acknowledgements
We thank B. Sakmann and P. Andersen for discussions, R.J. Wenthold for antibodies, F. Schwenk for the deleter mouse, R. Pfeffer, A. Herold, M. Lang for technical assistance and M. Belovska, M. Kosma, S. Kranz for dendritic tree analysis. K.K. was recipient of an EMBO long–term fellowship. H.–C.K. was supported by Boehringer Ingelheim. This work was funded, in part, by grants from HFSP, the Volkswagenstiftung, the German Chemical Society and an unrestricted grant from Bristol–Meyers Squibb.
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Feldmeyer, D., Kask, K., Brusa, R. et al. Neurological dysfunctions in mice expressing different levels of the Q/R site–unedited AMPAR subunit GluR–B. Nat Neurosci 2, 57–64 (1999). https://doi.org/10.1038/4561
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DOI: https://doi.org/10.1038/4561
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