Nature Neuroscience
2, 57 - 64 (1999)
doi:10.1038/4561
Neurological dysfunctions in mice expressing different levels of the Q/R site−unedited AMPAR subunit GluR−BDirk Feldmeyer2, Kalev Kask1, 4, Rossella Brusa1, 5, Hans−Christian Kornau1, 6, Rohini Kolhekar1, 6, Andrei Rozov2, Nail Burnashev2, Vidar Jensen3, Øivind Hvalby3, Rolf Sprengel1
& Peter H. Seeburg11
Department of Molecular Neurobiology, Max−Planck−Institute for Medical Research, Jahnstr. 29, 69120 Heidelberg, Germany
2
Department of Molecular Cell Physiology, Max−Planck−Institute for Medical Research, Jahnstr. 29, 69120 Heidelberg, Germany
3
Institute of Neurophysiology, University of OsloL, P.O. Box 1104 Blindern, N−0317 Oslo, Norway
4
Present address: AGY Therapeutics, Inc., c/o Tularik, Inc., Two Corporate Drive, South San Francisco, California 94080, USA
5
Present address: Schering Plough Research Institute, Via Olgettina 58, 20132, Milan, Italy
6
Present address: BASF−LYNX Bioscience AG, Im Neuenheimer Feld 515, 69120 Heidelberg, Germany
Correspondence should be addressed to Rolf Sprengel sprengel@mpimf−heidelberg.mpg.de
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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