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Cited by 431

The DOI matches its Crossref record; 3 of the 3 references it cites were found in a registry or an index.

Enhanced tonic GABAA inhibition in typical absence epilepsy

Open access
Cope, David W, Di Giovanni, Giuseppe, Fyson, Sarah J, Orbán, Gergely, Errington, Adam C, Lőrincz, Magor L, Gould, Timothy M, Carter, David A, Crunelli, Vincenzo·2009·Nature Medicine

Abstract

The cellular mechanisms underlying typical absence seizures, which characterize various idiopathic generalized epilepsies, are not fully understood, but impaired γ-aminobutyric acid (GABA)-ergic inhibition remains an attractive hypothesis. In contrast, we show here that extrasynaptic GABAA receptor–dependent 'tonic' inhibition is increased in thalamocortical neurons from diverse genetic and pharmacological models of absence seizures. Increased tonic inhibition is due to compromised GABA uptake by the GABA transporter GAT-1 in the genetic models tested, and GAT-1 is crucial in governing seizure genesis. Extrasynaptic GABAA receptors are a requirement for seizures in two of the best characterized models of absence epilepsy, and the selective activation of thalamic extrasynaptic GABAA receptors is sufficient to elicit both electrographic and behavioral correlates of seizures in normal rats. These results identify an apparently common cellular pathology in typical absence seizures that may have epileptogenic importance and highlight potential therapeutic targets for the treatment of absence epilepsy.

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Crossref · 10.1038/nm.2058

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Metadata

Authors
Cope, D. W., Di Giovanni, G., Fyson, S. J., Orbán, G., Errington, A. C., Lőrincz, M. L., Gould, T. M., Carter, D. A., & Crunelli, V.
Venue
Nature Medicine
Published
2009-11-22
Volume
15
Issue
12
Pages
1392-1398
ISSN
  • 1078-8956 (ISSN-L)
  • 1546-170X
OpenAlex
W1996957734
Cited by
431
References
3
FWCI
13.66
Type
journal article
Language
en
Open access
bronze

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