Comparisons between strychnine and penicillin epileptogenesis suggest that propagating epileptiform abnormalities require the potentiation of thalamocortical circuitry in neocortical layer 4.

Simultaneous recordings from three laminae within the cat visual cortex following differential intralaminar injections of strychnine (i) confirmed that low strychnine concentrations (5 mM) induce interictal-like epileptiform abnormalities (late responses) only when injected into superficial layers 2 and 3, (ii) revealed that these abnormalities are generated locally within these layers, and (iii) showed that they remain local phenomena by not spreading vertically into other cortical layers. Higher strychnine concentrations (20 mM), however, (iv) obscured these laminar differences by increasing layer 4 sensitivity to this agent in addition to the maximally sensitive superficial layers, and further (v) revealed nonlocal, vertically propagating, interictal-like abnormalities (late responses) following layer 4 injections which are preceded by an increase in thalamocortically mediated activity within this layer (enhanced physiologic responses). When penicillin was used as the convulsant, propagated interictal-like responses (late responses) induced in any layer were always preceded by a thalamocortically mediated response from layer 4 (enhanced physiologic responses); a condition clearly unlike the 5 mM but similar to the 20 mM strychnine foci observed in this study. These results suggest that convulsant action upon the thalamocortical circuitry of layer 4 is essential for the development of propagating as opposed to local epileptiform activity. Further, these results may also help explain why some cortical seizure disorders remain localized (focal) whereas others secondarily generalize to distal brain sites (i.e., complex partial seizures of extratemporal origin).