Interictal-ictal interactions and limbic seizure generation

Interictal discharges are used in clinical practice to localize the epilept ogenic focus in patients with partial epilepsy. However, the interaction be tween interictal and ictal discharges remains debatable. For instance, inte rictal events may lead to seizure onset in some models of epileptiform disc harge. By contrast, in other models, disappearance of interictal activity ( for example by activation of GABAB receptors) induces or potentiates ictal events. We have recently obtained new evidence for a control exerted by int erictal discharges on ictal activity in rodent combined slices of hippocamp us-entorhinal cortex. In this preparation continuous application of 4-amino pyridine induces: (i) interictal activity which initiates in CA3 and propag ates via CA1 and subiculum to the entorhinal cortex, and return to the hipp ocampus through the dentate gyrus; and (ii) ictal discharges, which origina te in the entorhinal cortex and propagate via the dentate gyrus to the hipp ocampus. Ictal discharges disappear over time, while synchronous interictal discharges continue to occur. Lesioning the Schaffer collaterals abolishes interictal discharges in CA1, entorhinal cortex and dentate gyrus and disc loses entorhinal ictal discharges that propagate, via the dentate gyrus, to the CA3 subfield, Interictal activity of CA3 origin also prevents the occu rrence of ictal events recorded in the entorhinal cortex in Mg2+-free mediu m. Moreover, in both models, ictal discharge generation in the entorhinal c ortex after Schaffer collateral cut is prevented by mimicking CA3 activity through rhythmic electrical stimulation of CA1 hippocampal outputs. Hence, our data demonstrate that hippocampus interictal discharges control the exp ression of electrographic seizures in entorhinal cortex. Sectioning the Sch affer collaterals may model the epileptic condition in which cell damage in the CA3 subfield results in loss of CA3 control over the entorhinal cortex . Hence, the functional integrity of hippocampal CA3 neurons may represent a critical control point in temporal lobe epilepsy.