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

[en] 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 γ-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 6-9 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 α3 subunit. SIGNIFICANCE: The data support the hypothesis that FS persistently alter neuronal excitability.

Disciplines :

Anatomy (cytology, histology, embryology...) & physiology

Author, co-author :

Avila Macaya, Ariel Salvatore ; Université de Liège - ULiège > Form. doc. sc. bioméd. & pharma.

Language :

English

Title :

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

Publication date :

2012

Journal title :

Epilepsia

ISSN :

0013-9580

eISSN :

1528-1167

Publisher :

Blackwell Science, Malden, United States - Massachusetts

Peer reviewed :

Peer Reviewed verified by ORBi

Additional URL :

http://www.ncbi.nlm.nih.gov/pubmed/23030508

Available on ORBi :

since 21 February 2013

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