Penicillin epileptogenesis in the rat: diffusion and the differential laminar sensitivity of the cortex cerebri.

When penicillin is applied electrophoretically from a fluid-filled microelectrode into the substance of the somatosensory cortex of the rat under urethane anaesthesia, the latent period for production of interictal epileptic spikes is least when the electrode lies 0.7 mm below the cortical surface. With low electrophoretic currents of --50 to 100 nA the increase in latent period as the tip of the electrode is placed further and further away from this level can be quantitatively accounted for by the time taken for penicillin to diffuse and to reach a threshold concentration throughout a critical mass of tissue at the 0.7 mm level. With these low currents, the generators of the interictal spikes are confined to a band of cortex centred at the 0.7 mm level. This is true even when the penicillin is applied away from the sensitive layer; in this circumstance the duration of electrophoresis needed to evoke interictal spikes is greater but when they do eventually appear the spikes are generated at the 0.7 mm layer. Histologically, the sensitive layer has been identified as the deep part of layer III. So far as the generation of interictal spikes is concerned, there is no evidence that, with low electrophoretic currents, penicillin has effects other than at the deep part of layer III; all the available evidence indicates that the penicillin has to diffuse to this layer and produces its effects there.