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Title: Experimental early-life febrile seizures induce changes in GABA(A)R-mediated neurotransmission in the dentate gyrus
Authors: Swijsen, Ann 
Avila, Ariel 
Brone, Bert 
Janssen, Daniel 
Hoogland, Govert 
Rigo, Jean-Michel 
Issue Date: 2012
Source: EPILEPSIA, 53 (11), p. 1968-1977
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.
Notes: [Swijsen, Ann; Avila, Ariel; Brone, Bert; Janssen, Daniel; Rigo, Jean-Michel] Hasselt Univ Transnat Univ Limburg, BIOMED Res Inst, Diepenbeek, Belgium. [Hoogland, Govert] Univ Med Ctr Maastricht, Sch Mental Hlth & Neurosci, Dept Neurosurg, Maastricht, Netherlands.
Keywords: Hyperthermia; Hippocampus; Epileptogenesis; gamma-Aminobutyric acid type A receptor; Whole-cell patch-clamp;Clinical Neurology; hyperthermia; hippocampus; epileptogenesis; gamma-aminobutyric acid type A receptor; whole-cell patch-clamp
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ISSN: 0013-9580
e-ISSN: 1528-1167
DOI: 10.1111/j.1528-1167.2012.03694.x
ISI #: 000310975400016
Category: A1
Type: Journal Contribution
Validations: ecoom 2014
Appears in Collections:Research publications

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