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Seizures in the developing brain result in a long-lasting decrease in GABA(B) inhibitory postsynaptic currents in the rat hippocampus.

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 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.
AuthorsLintao Qu, Richard Boyce, L Stan Leung
JournalNeurobiology of disease (Neurobiol Dis) Vol. 37 Issue 3 Pg. 704-10 (Mar 2010) ISSN: 1095-953X [Electronic] United States
PMID20026210 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright2009 Elsevier Inc. All rights reserved.
Chemical References
  • CGP 56999A
  • GABA Antagonists
  • GABA-B Receptor Antagonists
  • Phosphinic Acids
  • Receptors, GABA-B
  • gamma-Aminobutyric Acid
Topics
  • Action Potentials (drug effects, physiology)
  • Age Factors
  • Aging (physiology)
  • Animals
  • Animals, Newborn
  • CA1 Region, Hippocampal (growth & development, metabolism, physiopathology)
  • Dentate Gyrus (growth & development, metabolism, physiopathology)
  • Down-Regulation (physiology)
  • Epilepsy (metabolism, physiopathology)
  • GABA Antagonists (pharmacology)
  • GABA-B Receptor Antagonists
  • Hippocampus (growth & development, metabolism, physiopathology)
  • Inhibitory Postsynaptic Potentials (physiology)
  • Male
  • Neural Inhibition (physiology)
  • Neurons (drug effects, metabolism)
  • Organ Culture Techniques
  • Patch-Clamp Techniques
  • Phosphinic Acids (pharmacology)
  • Rats
  • Rats, Long-Evans
  • Receptors, GABA-B (metabolism)
  • Synapses (metabolism)
  • Synaptic Transmission (physiology)
  • Time
  • gamma-Aminobutyric Acid (metabolism)

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