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This Article Full Text Full Text (PDF) All Versions of this Article: 95/4/2446    most recent 01173.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via ISI Web of Science (2) Citing Articles via Google Scholar Google Scholar Articles by Kumar, S. S. Articles by Buckmaster, P. S. Search for Related Content PubMed PubMed Citation Articles by Kumar, S. S. Articles by Buckmaster, P. S.

GABA_A Receptor–Mediated IPSCs and 1 Subunit Expression Are Not Reduced in the Substantia Nigra Pars Reticulata of Gerbils With Inherited Epilepsy

¹Department of Comparative Medicine, ²Department of Neurology and Neurological Sciences, and ³Graduate Program in Neuroscience, Stanford University, Stanford, California

Submitted 7 November 2005; accepted in final form 9 January 2006

Domestic Mongolian gerbils, a model of inherited epilepsy, begin having spontaneous seizures at 1.5 mo of age, making it possible to evaluate them during epileptic and pre-epileptic stages. Previous studies have shown that GABA binding is reduced in the substantia nigra pars reticulata (SNr) of both epileptic and pre-epileptic gerbils compared with controls, suggesting that reduced expression of GABA_A receptors in SNr might be epileptogenic in this model. To test this hypothesis, we measured the expression of the GABA_A receptor 1 subunit, the dominant subunit expressed in the SNr, and evaluated GABA_A receptor–mediated postsynaptic currents in SNr neurons. GABA_A 1 subunit mRNA levels in substantia nigra–rich tissue from pre-epileptic animals were similar to controls, and immunocytochemistry for the 1 subunit showed similar strong expression in the SNr in both groups. Western analysis confirmed that expression of the 1 subunit protein was similar in substantia nigra–rich tissue from pre-epileptic and control gerbils. The frequency and amplitude of spontaneous inhibitory postsynaptic currents (IPSCs) and the frequency of miniature (m)IPSCs in SNr neurons of pre-epileptic gerbil were similar to those of controls. The amplitude of mIPSCs in the pre-epileptics was significantly larger than controls. Zolpidem, an 1 subunit–specific modulator of the GABA_A receptor, was equally efficacious in prolonging the decay time of mIPSCs in both groups. Hence, contrary to the predictions of the hypothesis, mRNA and protein expression levels of the major GABA_A receptor subunit were normal, and neurons of the SNr in pre-epileptic gerbils displayed normal or enhanced IPSC frequencies and amplitudes. Therefore reduced expression of GABA_A receptors in SNr is not likely to be an epileptogenic mechanism in this model.