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Downregulation of tonic GABA currents following epileptogenic stimulation of rat hippocampal cultures
Author(s) -
Qi Jinshun,
Yao Jun,
Fang Cheng,
Luscher Bernhard,
Chen Gong
Publication year - 2006
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2006.113134
Subject(s) - bicuculline , gabaergic , neuroscience , gabaa receptor , inhibitory postsynaptic potential , epileptogenesis , postsynaptic potential , neurotransmission , hippocampal formation , stimulation , gaba receptor antagonist , chemistry , gamma aminobutyric acid , tonic (physiology) , kainic acid , biology , receptor , glutamate receptor , biochemistry
Deficits in GABAergic inhibitory transmission are a hallmark of temporal lobe epilepsy and have been replicated in animal and tissue culture models of epilepsy. GABAergic inhibition comprises phasic and tonic inhibition that is mediated by synaptic and extrasynaptic GABA A receptors, respectively. We have recently demonstrated that chronic stimulation with cyclothiazide (CTZ) or kainic acid (KA) induces robust epileptiform activity in hippocampal neurons both in vitro and in vivo . Here, we report a downregulation of tonic GABA inhibition after chronic epileptogenic stimulation of rat hippocampal cultures. Chronic pretreatment of hippocampal neurons with CTZ or KA resulted in a marked reduction in GABAergic inhibition, as shown by a significant decrease in whole‐cell GABA currents and in the frequency of miniature inhibitory postsynaptic currents (mIPSCs). Interestingly, synaptically localized GABA A receptors remained relatively stable, as evidenced by the unaltered amplitude of mIPSCs, as well as the unchanged punctate immunoreactivity of γ2 subunit‐containing postsynaptic GABA A receptors. In contrast, tonic GABA currents, assessed either by a GABA A receptor antagonist bicuculline or a selective extrasynaptic GABA A receptor agonist THIP, were significantly reduced following epileptogenic stimulation. These results reveal a novel form of neural plasticity, that epileptogenic stimulation can selectively downregulate extrasynaptic GABA A receptors while leaving synaptic GABA A receptors unchanged. Thus, in addition to synaptic alteration of GABAergic transmission, regulation of tonic inhibition may also play an important role during epileptogenesis.