Journal article
Role of GluK1 Kainate Receptors in Seizures, Epileptic Discharges, and Epileptogenesis
The Journal of neuroscience, v 34(17), pp 5765-5775
23 Apr 2014
PMID: 24760837
Featured in Collection : UN Sustainable Development Goals @ Drexel
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.
Metrics
Details
- Title
- Role of GluK1 Kainate Receptors in Seizures, Epileptic Discharges, and Epileptogenesis
- Creators
- Brita Fritsch - University of California, DavisJanine Reis - National Institute of Neurological Disorders and StrokeMaciej Gasior - National Institute of Neurological Disorders and StrokeRafal M. Kaminski - National Institute of Neurological Disorders and StrokeMichael A. Rogawski - National Institute of Neurological Disorders and Stroke
- Publication Details
- The Journal of neuroscience, v 34(17), pp 5765-5775
- Publisher
- Society for Neuroscience
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology
- Web of Science ID
- WOS:000334929100005
- Scopus ID
- 2-s2.0-84899475895
- Other Identifier
- 991019173896804721
UN Sustainable Development Goals (SDGs)
This publication has contributed to the advancement of the following goals:
InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Neurosciences