Epileptiform afterdischarges and chemical responsiveness of cortical neurones

Abstract

The chemical responsiveness of single cortical neurones to microiontophoretic application of an excitatory and inhibitory putative neuro-transmitter was tested in cats during epileptiform afterdischarges or sustained afterdischarges, and at the end of epileptiform activity. Many cells which are presumably participating in an afterdischarge appear to lose chemical sensitivity to glutamate and exhibit altered responsiveness to GABA. The lack of effect of these substances during an afterdischarge suggests that many cells are in a state of “depolarization block”. The excitation observed after GABA application suggests that cells, upon sufficient hyperpolarization, are able to respond to the excitatory synaptic input. The conditions which lead to cessation of an afterdischarge can be attenuated, artificially, for periods of more than 1 h. Both surface clonic waves and epileptiform bursts of single cortical units can be entrained by relatively weak electrical stimuli applied at low frequencies during the clonic phase. Iontophoretic application of glutamate during this time reduces the firing rate while GABA is less effective in depressing the extracellular discharge. The data suggest that cells within the stimulated focus are in a state of partial “depolarization block” during which time activation by surface stimuli is facilitated. The termination of epileptiform activity is followed by a depression of unit firing which can be overcome by increasing the administration of a depolarizing amino acid. The data provide presumptive evidence that this period is due to hyperpolarization of cortical cells which were previously involved in the afterdischarge. The results also suggest that there is a reduced effectiveness of an inhibitory transmitter in ‘controlling’ repetitive activity of cells during an afterdischarge and that prolonged activation allows the maintenance of epileptiform activity.