Abstracts

Recent findings suggest that a shift in GABA actions from inhibition to excitation may contribute to human interictal epileptiform activity. To investigate this relationship in more detail, we tested whether excitatory effects of endogenously released GABA measured at the network level correlated with the presence of spontaneous epileptiform activity in slices prepared from rats rendered chronically epileptic by prior administration of kainic acid. We used multichannel extracellular recordings of population activity and multiple unit activity in acute hippocampal slices prepared from 6 month old rats that had been treated with kainate at 6 weeks of age and had spontaneous seizures. We checked for the presence of spontaneous CA3 bursts in control solutions and then blocked glutamate receptors and measured network action potentials before and after blockade of GABA[sub]A[/sub] receptors. A strong correlation was found between the GABA-mediated excitation (decreased action potential frequency after block of GABA[sub]A[/sub] receptors) and the presence of spontaneous epileptiform discharges in area CA3. Excitatory effects of GABA[sub]A[/sub] receptor activation are likely to contribute to the generation of spontaneous interictal epileptiform activity. Alternatively, interictal activity may set in motion activity-dependent mechanisms that shift EGABA such that GABA[sub]A[/sub] receptor activation becomes excitatory. Both of these processes may be active concurrently. (Supported by the NIH-NINDS grant.)