PT  - JOURNAL ARTICLE
AU  - Heinz E. Krestel
AU  - Derya R. Shimshek
AU  - Vidar Jensen
AU  - Thomas Nevian
AU  - Jinhyun Kim
AU  - Yu Geng
AU  - Thomas Bast
AU  - Antoine Depaulis
AU  - Kai Schonig
AU  - Frieder Schwenk
AU  - Hermann Bujard
AU  - Øivind Hvalby
AU  - Rolf Sprengel
AU  - Peter H. Seeburg
TI  - A Genetic Switch for Epilepsy in Adult Mice
AID  - 10.1523/JNEUROSCI.4579-03.2004
DP  - 2004 Nov 17
TA  - The Journal of Neuroscience
PG  - 10568--10578
VI  - 24
IP  - 46
4099  - http://www.jneurosci.org/content/24/46/10568.short
4100  - http://www.jneurosci.org/content/24/46/10568.full
SO  - J. Neurosci.2004 Nov 17; 24
AB  - Premature death from seizures afflicts gene-targeted mice expressing the Q/R site-unedited glutamate receptor subunit GluR-B(Q) of AMPA receptors in central neurons. Early seizure-related death has now been circumvented by a genetic switch that restricts GluR-B(Q) expression to forebrain principal neurons from postnatal stages onward, prominently in hippocampus and striatum and less so in cortex and amygdala. When switched on, functional receptor incorporation of GluR-B(Q) could be demonstrated by imaging evoked AMPA channel-mediated spinous Ca2+ transients in CA1 pyramidal cells. Sustained GluR-B(Q) expression in adult mice led to smaller excitatory postsynaptic responses in the CA1 region with unchanged presynaptic fiber excitability. Notably, despite the smaller excitatory response, the CA1 cells exhibited a reduced population spike threshold, which might underlie the spontaneous manifestations of epilepsy, including myocloni and generalized seizures with limbic components, observed by synchronous video monitoring and electroencephalographic recordings. No neuropathological symptoms developed when GluR-B(Q) expression was restricted to only hippocampal neurons. Our results show that seizure susceptibility is triggered by GluR-B(Q) expression also in the adult brain and that circuit hyperexcitability is not an immediate consequence of GluR-B(Q) but requires yet unknown downstream events, likely to be induced by non-Hebbian plasticity from Ca2+-permeable AMPA channels in principal neurons.