Partial suppression of GABAA-mediated inhibition induces spatially restricted epileptiform activity in guinea pig neocortical slices.

The spatio-temporal distribution of evoked activity in guinea pig neocortical slices was investigated during partial suppression of gamma-aminobutyric acid (GABA)A-mediated synaptic inhibition with different concentrations of bicuculline. Activity patterns were recorded by use of a voltage-sensitive dye and a fast optical recording technique. At non-epileptogenic concentrations of bicuculline (0.6-2.5 microM), evoked potentials were of longer duration and larger amplitude, but the spatial extent of spread in the horizontal direction was unaffected. At threshold epileptogenic concentrations of bicuculline (1.25-5 microM), spatially restricted epileptiform activity developed at a distance from the stimulation site which was clearly separated from potentials with non-epileptic characteristics close to the stimulation site. It is concluded that, under moderate disinhibition, stimulus-evoked activity has a suppressive effect on spread and development of epileptiform activity, probably through synchronous activation of still-functioning inhibitory circuits.