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Seizures in the developing brain result in a long-lasting decrease in GABAB inhibitory postsynaptic currents in the rat hippocampus
Ist Teil von
Neurobiology of disease, 2010-03, Vol.37 (3), p.704-710
Ort / Verlag
Elsevier
Erscheinungsjahr
2010
Quelle
Alma/SFX Local Collection
Beschreibungen/Notizen
Abstract Whether seizures in the developing brain cause long-term changes in the mature brain has been debated. We tested the hypothesis that a model of early-life seizures, induced by systemic injection of a GABAB receptor antagonist CGP56999A in immature rats, decreased GABAB receptor-mediated inhibitory postsynaptic currents (IPSCs) in the hippocampus of adolescent rats. Whole-cell recordings were made in CA1 pyramidal cells and dentate gyrus (DG) granule cells in vitro , 30–45 days after the rats had seizures induced by CGP56999A (1–1.5 mg/kg i.p.) or control saline injection on postnatal day 15. GABAB receptor-mediated IPSCs were reduced in DG neurons but not in CA1 neurons of early-life seizure rats as compared to controls. Additionally, hippocampal neurons of early-life seizure rats, as compared to those in control rats, showed a more depolarized resting membrane potential in both CA1 and DG, and a larger input resistance but reduced spike frequency adaptation in DG neurons. In conclusion, early-life seizures result in a long-lasting reduction in GABAB receptor-mediated transmission in DG principal neurons and depolarization in CA1 and DG principal neurons. These alterations are expected to increase seizure susceptibility in the adult brain.