Abstracts

Rationale: Little is known about the anatomical and network properties of the neocortex that contribute to the generation of epileptic discharges. We have previously found that both human epileptic neocortex and neocortex from rats that develop epileptic discharges produce activation of key signaling pathways in the most superficial layers of the neocortex. Here we have determined the neurophysiological correlates of these layer-specific changes using microelectrode array extracellular recordings from both normal rats and rats who generate spontaneous epileptic discharges using the tetanus toxin model. Methods: Microarray extracellular recordings were performed in both na ve animals as well as those who have spontaneous epileptiform discharges in vivo. Slices were stimulated with low magnesium and 100 ?M 4-Aminopyridine. Electrodes were localized to specific cortical layers and those exhibiting discharges with the highest negative polarity voltage were mapped to the corresponding zone in the cortical slice. Results: While cortical slices from young animals develop both interictal and ictal rhythms diffusely across the cortex, adult slices had less activity overall that was highly restricted to the convexity of the cortical surface and clustered in three distinct areas, along the parasagittal, lateral convexity , and inferior lateral cortex . A surprisingly high density of epileptic discharges were seen over the superficial cortical layers, in the same regions we have seen activation of epileptic signaling pathways in humans. Slices from animals with spontaneous epileptic discharges in vivo showed significantly more activity and more spread of the epileptic discharges than those without epileptic activity.Conclusions: The laminar and spatial organization of the neocortex can be revealed from acute multielectrode array slice recordings. The presence of distinct zones of hyperexcitability is a novel finding that likely reflects a fundamental difference in network organization that leads to different epileptic activities in different brain regions and is further altered following the development of an epileptic focus. These results also show that while epileptiform discharges can be generated in different cortical layers, the majority of discharges originated from superficial cortical layers, especially from layer 1.