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Rapid and long‐term alterations of hippocampal GABA B receptors in a mouse model of temporal lobe epilepsy
Author(s) -
Straessle Andrea,
Loup Fabienne,
Arabadzisz Dimitrula,
Ohning Gordon V.,
Fritschy JeanMarc
Publication year - 2003
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1046/j.1460-9568.2003.02964.x
Subject(s) - dentate gyrus , epileptogenesis , kainic acid , hippocampal formation , granule cell , neuroscience , gabaa receptor , receptor , biology , postsynaptic potential , interneuron , hippocampus , temporal lobe , epilepsy , glutamate receptor , inhibitory postsynaptic potential , biochemistry
Alterations of γ‐aminobutyric acid (GABA) B receptor expression have been reported in human temporal lobe epilepsy (TLE). Here, changes in regional and cellular expression of the GABA B receptor subunits R1 (GBR1) and R2 (GBR2) were investigated in a mouse model that replicates major functional and histopathological features of TLE. Adult mice received a single, unilateral injection of kainic acid (KA) into the dorsal hippocampus, and GABA B receptor immunoreactivity was analysed between 1 day and 3 months thereafter. In control mice, GBR1 and GBR2 were distributed uniformly across the dendritic layers of CA1–CA3 and dentate gyrus. In addition, some interneurons were labelled selectively for GBR1. At 1 day post‐KA, staining for both GBR1 and GBR2 was profoundly reduced in CA1, CA3c and the hilus, and no interneurons were visible anymore. At later stages, the loss of GABA B receptors persisted in CA1 and CA3, whereas staining increased gradually in dentate gyrus granule cells, which become dispersed in this model. Most strikingly, a subpopulation of strongly labelled interneurons reappeared, mainly in the hilus and CA3 starting at 1 week post‐KA. In double‐staining experiments, these cells were selectively labelled for neuropeptide Y. The number of GBR1‐positive interneurons also increased contralaterally in the hilus. The rapid KA‐induced loss of GABA B receptors might contribute to epileptogenesis because of a reduction in both presynaptic control of transmitter release and postsynaptic inhibition. In turn, the long‐term increase in GABA B receptors in granule cells and specific subtypes of interneurons may represent a compensatory response to recurrent seizures.