Epileptiform propagation patterns mediated by NMDA and non-NMDA receptors in rat neocortex

Purpose: The neocortex can generate various forms of epileptiform activity, including one that depends on N-methyl-D-aspartate (NMDA)-type glutamate r eceptors (NMDARs), and another dependent on non-NMDA-type (AMPA) glutamate receptors (AMPARs). Previous work in vitro suggests that both forms of acti vity are initiated by neurons of layer 5, but the spatial patterns of horiz ontal propagation have been studied only for the AMPAR form. We have tested the hypothesis that both types of epileptiform activity spread via common pathways in one cortical layer, suggesting that lamina-specific interventio n might selectively interrupt both. Methods: Slices of rat somatosensory cortex were maintained in vitro and tr eated with the gamma-aminobutyric acid type A (GABA(A))-receptor antagonist picrotoxin. Single all-or-none epileptiform discharges were evoked with an electrical stimulus, and extracellular microelectrodes were used to track the vertical and lateral spread of the discharges. Results: In both high and low concentrations of picrotoxin, the non-NMDAR a ntagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) completely blocked pr opagation, whereas the NMDAR antagonist D-2-amino-5-phosphonovaleric acid ( DAPV) only shortened the duration of discharges. When extracellular [Mg2+] was reduced in the presence of picrotoxin and CNQX, NMDAR-dependent epilept iform discharges could be initiated. NMDAR-dependent discharges spread at a bout one fifth the conduction velocity of AMPAR-dependent events. Analysis of spatiotemporal field-potential patterns suggested that both NMDAR- and A MPAR-mediated propagation involved early activity in layers 5 and 6, follow ed by larger-amplitude activity in upper cortical layers along the path of propagation. Conclusions: Our results imply that a common pathway mediates the propagati on of these two forms of epileptiform activity, and suggests that lamina-sp ecific surgical intervention might maximize anticonvulsant effect while min imally disrupting cortical function.