Mechanism of electrographic seizure generation in the hippocampal slice in Mg 2+-free medium: the role of GABA a inhibition

Abstract

We recently have described a new model of ictal-like electrographic activity in the hippocampal slice. When magnesium is eliminated from the medium bathing the hippocampal slice, spontaneously occurring electrical events which closely resemble electrographic seizures can be recorded extracellularly from area CA3. In order to begin to understand the mechanisms of initiation and termination of these seizures, the present study investigated the role of GABA a-mediated inhibition in these processes. Prior to the onset of a seizure recorded from stratum pyramidale of CA3, a twin-pulse stimulus to stratum radiatum of CA3 evoked twin EPSPs. Following the seizure, the same stimulation triggered a strong epileptiform burst. This is consistent with the known reduction of GABA a inhibition after seizures in vivo. Addition of bicuculline, picrotoxin, or penicillin, which reduce the efficacy of GABA a -mediated inhibition in this system, caused triggered epileptiform bursting to occur prior to the seizure as well. They also lowered the threshold for the production of seizures, facilitating their spontaneous occurrence or elicitation by fewer stimulus pulses. This suggests that the GAB A a inhibition present in magnesium-free (0-Mg) plus baclofen medium tends to suppress the onset of seizures and raises the seizure threshold. However, these drugs did not prolong the ictal events. This suggests that in this model, GABA a-mediated inhibition is not responsible for termination of the seizure-like activity. Although there is some potentiation of the tonic firing phase of the seizures under these conditions, there is no gross change in the morphology of the events when inhibition is suppressed. In this model, therefore, GABA a-mediated inhibition plays a limited role in determining the structure and duration of the ictal events, but may contribute to the seizure threshold.