Abstract : Kainate generates in adult hippocampal neurons a seizure but also a massive excitation of interneurons and a dramatic increase of the inhibitory drive that impinges on principal cells. This "overinhibition" is largely mediated by GluR5-containing kainate receptors that are enriched on interneurons. Here, using the neonatal intact hippocampus in vitro and the triple chamber, we first show that this mechanism is fully operative in neonatal neurons. We then report that application to one hippocampus of (RS)-2-amino-3-(5-tert-butyl-3-hydroxy-4-isoxazolyl)propionic acid-a relatively selective agonist of GluR5 containing kainate receptors-depresses the propagation of seizure generated in the opposite hippocampus by a convulsive agent. We conclude that the selective excitation of interneurons by GluR5-containing kainate receptor agonists opens a new therapeutic approach for the epilepsies.
https://www.hal.inserm.fr/inserm-00484867 Contributor : Roman TyzioConnect in order to contact the contributor Submitted on : Wednesday, May 19, 2010 - 1:09:09 PM Last modification on : Thursday, January 27, 2022 - 10:34:04 AM Long-term archiving on: : Wednesday, November 30, 2016 - 10:30:55 PM
Ilgam Khalilov, June C. Hirsch, Rosa Cossart, yehezkel Ben-Ari. Paradoxical anti-epileptic effects of a GluR5 agonist of kainate receptors.. Journal of Neurophysiology, American Physiological Society, 2002, 88 (1), pp.523-7. ⟨inserm-00484867⟩