Phases in the development of a penicillin epileptiform focus in rat neocortex

Somatosensory evoked potentials and potentials evoked by direct cortical stimulation were recorded from layer IV of the somatosensory area of the cerebral cortex in urethane anaesthetised rats. Penicillin was expelled electrophoretically from the tip of a drug-filled micropipette at constant rates into layer IV. Small fluxes of penicillin (with electrophoretic currents of -50 to -90 nA) resulted in the appearance, after a delay of 1–2 min, of an enhancement of amplitude in the voltage of both types of evoked potential, unaccompanied by any prolongation of the waveform or spontaneous focal epileptiform discharges. The amplitude of the enhanced evoked potential exhibited a strength-response curve which was a scaled-up version of the curve before penicillin, the scaling factor reflecting the enhancement of amplitude. As the interval between a pair of stimuli was increased, the magnitude of the response to the second stimulus recovered, following a time course similar to that before penicillin. With larger fluxes of penicillin (with electrophoretic currents of -250 to -1000 nA) the amplitude of evoked potentials rose more rapidly and to a higher level; as the concentration of penicillin rose, this enhancement of amplitude led into a second phase, in which there was additionally an increase in the duration of the evoked potentials and the appearance of spontaneous epileptiform discharges. The evoked potentials in this situation showed physiological properties different from those before penicillin application. The strength-response curve exhibited a discontinuity, indicating the evoked potential to be the sum of a physiological response and an epileptiform discharge, the former being graded with stimulus strength and the latter being all or none. With paired stimuli, the response to the test stimulus was profoundly depressed for long conditioning-test intervals by comparison with the relatively rapid recovery exhibited by normal brain. When a cuboid of cortex measuring 0.6 mm² or less was partially isolated subpially by incisions extending through the upper half of the cortical mantle, all the features of hyperexcitability produced by penicillin in intact cortex were blocked. This shows that even the simple enhancement of evoked potentials, which is the earliest indicator of hypersynchronous activity, differs from an exaggeration of normal evoked activity in requiring a larger community of neurones with their horizontal intracortical connections intact.