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  A genetic switch for epilepsy in adult mice

Krestel, H. E., Shimshek, D. R., Jensen, V., Nevian, T., Kim, J.-H., Geng, Y., et al. (2004). A genetic switch for epilepsy in adult mice. The Journal of Neuroscience, 24(46), 10568-10578. doi:10.1523/JNEUROSCI.4579-03.2004.

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Genre: Journal Article
Alternative Title : A genetic switch for epilepsy in adult mice

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 Creators:
Krestel, Heinz Eric1, Author           
Shimshek, Derya R.1, Author           
Jensen, Vidar, Author
Nevian, Thomas2, Author           
Kim, Jin-Hyun, Author
Geng, Yu, Author
Bast, Thomas, Author
Depaulis, Antoine, Author
Schonig, Kai, Author
Schwenk, Frieder, Author
Bujard, Hermann, Author
Hvalby, Øivind, Author
Sprengel, Rolf1, Author           
Seeburg, Peter H.1, Author           
Affiliations:
1Department of Molecular Neurobiology, Max Planck Institute for Medical Research, Max Planck Society, ou_1497704              
2Department of Cell Physiology, Max Planck Institute for Medical Research, Max Planck Society, ou_1497701              

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Free keywords: Hippocampus, temporal Cre regulation, altered AMPA receptors, RNA editing, spinous calcium transients
 Abstract: 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.

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Language(s): eng - English
 Dates: 2004-08-272003-06-112004-09-302004-11-17
 Publication Status: Issued
 Pages: 10
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Degree: -

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Title: The Journal of Neuroscience
  Other : J. Neurosci.
Source Genre: Journal
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Publ. Info: Baltimore, MD : The Society
Pages: - Volume / Issue: 24 (46) Sequence Number: - Start / End Page: 10568 - 10578 Identifier: ISSN: 0270-6474
CoNE: https://pure.mpg.de/cone/journals/resource/954925502187