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.
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Authors | Lintao Qu, Richard Boyce, L Stan Leung |
Journal | Neurobiology of disease
(Neurobiol Dis)
Vol. 37
Issue 3
Pg. 704-10
(Mar 2010)
ISSN: 1095-953X [Electronic] United States |
PMID | 20026210
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | 2009 Elsevier Inc. All rights reserved. |
Chemical References |
- CGP 56999A
- GABA Antagonists
- GABA-B Receptor Antagonists
- Phosphinic Acids
- Receptors, GABA-B
- gamma-Aminobutyric Acid
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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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