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: D Feldmeyer, K Kask, R Brusa, H C Kornau, R Kolhekar, A Rozov, N Burnashev, V Jensen, O Hvalby, R Sprengel, P H Seeburg
• Journal: Nature neuroscience (Nat Neurosci) Vol. 2 Issue 1 Pg. 57-64 (Jan 1999) ISSN: 1097-6256 [Print] United States
• PMID: 10195181 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Receptors, AMPA
• Receptors, Glutamate
• glutamate receptor type B
• Calcium

Topics

• Alleles
• Animals
• Brain (pathology)
• Calcium (metabolism, physiology)
• Electric Conductivity
• Gene Expression (physiology)
• Hippocampus (physiopathology)
• Long-Term Potentiation (physiology)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Transgenic (genetics)
• Nervous System Diseases (genetics)
• Neural Pathways (physiopathology)
• Phenotype
• Receptors, AMPA (physiology)
• Receptors, Glutamate (genetics)