Role of GluK1 kainate receptors in seizures, epileptic discharges, and epileptogenesis

Brita Fritsch, Janine Reis, Maciej Gasior, Rafal M. Kaminski, Michael A Rogawski

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

Kainate receptors containing the GluK1 subunit have an impact on excitatory and inhibitory neurotransmission in brain regions, such as the amygdala and hippocampus, which are relevant to seizures and epilepsy. Here we used 2-amino-3-(3-hydroxy-5-tert-butylisoxazol-4-yl) propanoic acid (ATPA), a potent and selective agonist of kainate receptors that include the GluK1 subunit, in conjunction with mice deficient in GluK1 and GluK2 kainate receptor subunits to assess the role of GluK1 kainate receptors in provoking seizures and in kindling epileptogenesis. We found that systemic ATPA, acting specifically via GluK1 kainate receptors, causes locomotor arrest and forelimb extension (a unique behavioral characteristic of GluK1 activation) and induces myoclonic behavioral seizures and electrographic seizure discharges in the BLA and hippocampus. In contrast, the proconvulsant activity of systemic AMPA, kainate, and pentylenetetrazol is not mediated by GluK1 kainate receptors, and deletion of these receptors does not elevate the threshold for seizures in the 6 Hz model. ATPA also specifically activates epileptiform discharges in BLA slices in vitro via GluK1 kainate receptors. Olfactory bulb kindling developed similarly in wild-type, GluK1, and GluK2 knock-out mice, demonstrating that GluK1 kainate receptors are not required for epileptogenesis or seizure expression in this model. We conclude that selective activation of kainate receptors containing the GluK1 subunit can trigger seizures, but these receptors are not necessary for seizure generation in models commonly used to identify therapeutic agents for the treatment of epilepsy.

Original languageEnglish (US)
Pages (from-to)5765-5775
Number of pages11
JournalJournal of Neuroscience
Volume34
Issue number17
DOIs
StatePublished - 2014

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Keywords

  • ATPA
  • BLA
  • Epilepsy
  • Kainate receptor
  • Kindling
  • Seizure

ASJC Scopus subject areas

  • Neuroscience(all)

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