Neurological dysfunctions in mice expressing different levels of the Q/R site–unedited AMPAR subunit GluR–B
Copyright policy )Neurological dysfunctions in mice expressing different levels of the Q/R site–unedited AMPAR subunit GluR–B
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.
- University of Oslo Norway
- Max Planck Institute for Medical Research Germany
- Max Planck Society Germany
Male, Long-Term Potentiation, Electric Conductivity, Brain, Gene Expression, Mice, Transgenic, Hippocampus, Mice, Inbred C57BL, Mice, Phenotype, Receptors, Glutamate, Neural Pathways, Animals, Calcium, Receptors, AMPA, Nervous System Diseases, Alleles
Male, Long-Term Potentiation, Electric Conductivity, Brain, Gene Expression, Mice, Transgenic, Hippocampus, Mice, Inbred C57BL, Mice, Phenotype, Receptors, Glutamate, Neural Pathways, Animals, Calcium, Receptors, AMPA, Nervous System Diseases, Alleles
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