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.

journal_name

Neurobiol Dis

journal_title

Neurobiology of disease

authors

Qu L,Boyce R,Leung LS

doi

10.1016/j.nbd.2009.12.009

subject

Has Abstract

pub_date

2010-03-01 00:00:00

pages

704-10

issue

3

eissn

0969-9961

issn

1095-953X

pii

S0969-9961(09)00364-7

journal_volume

37

pub_type

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