GABA(A) ALPHA-2 MESSENGER-RNA LEVELS ARE DECREASED FOLLOWING INDUCTION OF SPONTANEOUS EPILEPTIFORM DISCHARGES IN HIPPOCAMPAL-ENTORHINAL CORTICAL SLICES

Exposure of hippocampal slices to Mg2+ free media (0 Mg) has been show n to trigger full production of stimulus-induced seizure activity afte r restoration of physiological conditions [1]. In the present study em ploying hippocampal entorhinal cortical slices (HEC), spontaneous epil eptiform discharges (SEDs) were induced using 0 Mg treatment following the return of the slices to physiological conditions. To evaluate the effect of sustained epileptiform activity on gene expression in this HEC slice preparation, changes in mRNA levels of the GABA(A) alpha 1 a nd alpha 2 and beta CaM Kinase II subunits were measured using in situ hybridization. HEC slices were incubated in oxygenated artificial cer ebrospinal fluid (ACSF) in the presence or absence of Mg2+ for 3 h, th en placed in oxygenated ACSF containing Mg2+ for up to 3 h. Control sl ices were maintained in Mg2+ containing ACSF for up to 6 h. Recurrent SEDs were observed in 0 Mg pre-treated slices while no epileptiform di scharges were seen in control slices. Following induction of SEDs by 0 Mg pre-treatment, a significant decrease in mRNA encoding GABA(A) alp ha 2 was found in the CA1, CA2, CA3 and dentate gyrus (DG) regions of the hippocampus for up to 3 h after treatment. Levels of mRNA for GABA (A) alpha 1 and beta CaM Kinase II were not affected. The results docu ment a decrease in GABA(A) alpha 2 gene expression following the induc tion of SEDs in the HEC slice preparation and suggest that rapid chang es in neuronal gene expression may contribute to long lasting excitabi lity changes associated with the induction of epilepsy.