Experimental early-life febrile seizures induce changes in GABA(A)R-mediated neurotransmission in the dentate gyrus

Ann Swijsen, Ariel Avila, Bert Brone, Daniel Janssen, Govert Hoogland, Jean-Michel Rigo*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

10 Citations (Web of Science)

Abstract

Purpose: Febrile seizures (FS), the most frequent seizure type during childhood, have been linked to temporal lobe epilepsy (TLE) in adulthood. Yet, underlying mechanisms are still largely unknown. Altered gamma-aminobutyric acid (GABA)ergic neurotransmission in the dentate gyrus (DG) circuit has been hypothesized to be involved. This study aims at analyzing whether experimental FS change inhibitory synaptic input and postsynaptic GABA(A)R function in dentate granule cells. Methods: We applied an immature rat model of hyperthermia (HT)induced FS. GABA(A)R-mediated neurotransmission was studied using whole-cell patch-clamp recordings from dentate granule neurons in hippocampal slices within 69 days post-HT. Key Findings: Frequencies of spontaneous inhibitory postsynaptic currents (sIPSCs) were reduced in HT rats that had experienced seizures, whereas sIPSC amplitudes were enhanced. Whole-cell GABA responses revealed a doubled GABA(A)R sensitivity in dentate granule cells from HT animals, compared to that of normothermic (NT) controls. Analysis of sIPSCs and whole-cell GABA responses showed similar kinetics in postsynaptic GABA(A)Rs of HT and NT rats. quantitative real-time polymerase chain reaction (qPCR) experiments indicated changes in DG GABA(A)R subunit expression, which was most pronounced for the alpha 3 subunit. Significance: The data support the hypothesis that FS persistently alter neuronal excitability.
Original languageEnglish
Pages (from-to)1968-1977
JournalEpilepsia
Volume53
Issue number11
DOIs
Publication statusPublished - Nov 2012

Keywords

  • Hyperthermia
  • Hippocampus
  • Epileptogenesis
  • gamma-Aminobutyric acid type A receptor
  • Whole-cell patch-clamp

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