Seizures in the developing brain result in a long-lasting decrease in GABA(B) inhibitory postsynaptic currents in the rat hippocampus.
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 GABA(B) receptor antagonist CGP56999A in immature rats, decreased GABA(B) 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. GABA(B) 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 GABA(B) 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.
Qu
Lintao
L
Graduate Program in Neuroscience, University of Western Ontario, London, Canada N6A 5C1.
Boyce
Richard
R
Leung
L Stan
LS
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000367:Age Factors; D000375:Aging / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D056547:CA1 Region, Hippocampal / Q000254:growth & development / Q000378:metabolism / Q000503:physiopathology; D018891:Dentate Gyrus / Q000254:growth & development / Q000378:metabolism / Q000503:physiopathology; D015536:Down-Regulation / Q000502:physiology; D004827:Epilepsy / Q000378:metabolism* / Q000503:physiopathology; D018756:GABA Antagonists / Q000494:pharmacology; D058788:GABA-B Receptor Antagonists; D006624:Hippocampus / Q000254:growth & development / Q000378:metabolism* / Q000503:physiopathology; D053444:Inhibitory Postsynaptic Potentials / Q000502:physiology; D008297:Male; D009433:Neural Inhibition / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D010721:Phosphinic Acids / Q000494:pharmacology; D051381:Rats; D020318:Rats, Long-Evans; D018080:Receptors, GABA-B / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology*; D013995:Time; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
C102659:CGP 56999A; D018756:GABA Antagonists; D058788:GABA-B Receptor Antagonists; D010721:Phosphinic Acids; D018080:Receptors, GABA-B; D005680:gamma-Aminobutyric Acid