Abstracts

Rationale: Most research on basic mechanisms of epilepsy has been performed through recordings only by a limited number of electrodes in temporal lobe slices of immature young animals. Recording discharges simultaneously from multiple electrodes can provide novel insight on the spatial organization of epileptic foci. We are using arrays of multiple electrodes to characterize mechanisms of adult chronic neocortical epilepsy.Methods: Three adult rats were injected with tetanus toxin in the left somatosensory cortex and developed spontaneous in vivo EEG discharges. Discharges prevailed over the right hemisphere (secondary focus) than over the left (primary focus). 16 somatosensory cortex slices were obtained from these three animals and epileptic discharges were induces by perfusion with 4 Amino-pyridine in a zero Mg medium. Recordings were performed through Multiple Electrode Arrays. Controls were 17 slices from 4 normal animals.Results: In normal rats slices discharges are expressed over several small scale foci while epileptic rats ictal discharges exhibit broader spreading both in the site of injection and in the contralateral one. Spread is more evident over the barrel cortex of epileptic rats. Interictal discharges and seizures exhibit higher voltages only in the primary focus (site of injection) (p<0.05). In the secondary focus interictal discharges originate mostly from supragranular layers (p<0.05). Interictal discharges zones exhibited an irregular, jagged contour while zones exhibiting rhythmic repetitive activity exhibited a uniform, regular perimeter. Initiations sites and propagation pathways of discharges recurrently shifted, as different sub-regions of a focus can initiate independently the discharge. Discharges propagation from barrel cortex into the forelimb somatosensory cortex follows a pathway over layer IV, skipping superficial laminae of dysgranular cortex, indicating that propagation follows a defined anatomical cytoarchitectonical path.Conclusions: Features of the intrinsic hyper-excitability of a chronic neocortical focus survive the severing of connections that occurs when brain slices are cut: there is no enhancement of discharges’ rates but rather increase in voltage and wider spreading, consistent with more synapses synchronizing rather than increase in bursting initiating discharges. A chronic epileptic focus consists in a multiplication of small zones of discharges. There are also specific properties distinguishing primary and secondary epileptic foci: a primary focus shows higher voltage discharges and more activity over deep laminae; a secondary focus shows enhancement of activity leading from supragranular laminae.