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 GABAa-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 GABAa inhibition after
seizures in vivo. Addition of
bicuculline,
picrotoxin, or
penicillin, which reduce the efficacy of GABAa-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 GABAa 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, GABAa-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, GABAa-mediated inhibition plays a limited role in determining the structure and duration of the ictal events, but may contribute to the seizure threshold.