Activation of extrasynaptic GABAA receptors inhibits cyclothiazide-induced epileptiform activity in hippocampal CA1 neurons

Li Wan, Xu Liu, Zheng Wu, Wanting Ren, Shuzhen Kong, Raya Abou Dargham, Longzhen Cheng, Yun Wang

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Extrasynaptic GABAA receptors (GABAARs)-mediated tonic inhibition is reported to involve in the pathogenesis of epilepsy. In this study, we used cyclothiazide (CTZ)-induced in vitro brain slice seizure model to explore the effect of selective activation of extrasynaptic GABAARs by 4,5,6,7-tetrahydroisoxazolo[5,4-c] pyridine-3-ol (THIP) on the CTZ-induced epileptiform activity in hippocampal neurons. Perfusion with CTZ dose-dependently induced multiple epileptiform peaks of evoked population spikes (PSs) in CA1 pyramidal neurons, and treatment with THIP (5 μmol/L) significantly reduced the multiple PS peaks induced by CTZ stimulation. Western blot showed that the δ-subunit of the GABAAR, an extrasynaptic specific GABAAR subunit, was also significantly down-regulated in the cell membrane 2 h after CTZ treatment. Our results suggest that the CTZ-induced epileptiform activity in hippocampal CA1 neurons is suppressed by the activation of extrasynaptic GABAARs, and further support the hypothesis that tonic inhibition mediated by extrasynaptic GABAARs plays a prominent role in seizure generation.

Original languageEnglish (US)
Pages (from-to)866-876
Number of pages11
JournalNeuroscience Bulletin
Volume30
Issue number5
DOIs
StatePublished - Sep 28 2014

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Physiology

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