Do interictal discharges promote or control seizures? Experimental evidence from an in vitro model of epileptiform discharge

Interictal and ictal discharges are recorded from limbic structures in temp oral lobe epilepsy patients. In clinical practice, interictal spikes are us ed to localize the epileptogenic area, but they also are assumed to promote ictal events. Here I review data obtained from combined slices of mouse hi ppocampus-entorhinal cortex that indicate an inverse relation between inter ictal and ictal events. In this preparation, application of 4-aminopyridine or Mg2+-free medium induce (a) interictal discharges that originated from CA3 and propagate (via the Schaffer collaterals) to CAI and entorhinal cort ex, to return to the hippocampus through the dentate area; and (b) ictal di scharges that initiate in the entorhinal cortex and propagate to the hippoc ampus via the dentate gyrus. Interictal activity occurs throughout the expe riment (up to 6 h), whereas ictal discharges disappear after 1-2 h. Schaffe r collateral cut abolishes interictal discharges in CAI, entorhinal cortex, and dentate and reestablishes entorhinal ictal discharges. Moreover, ictal discharge generation in the entorhinal cortex after Schaffer collateral cu t is prevented by mimicking CA3 activity with rhythmic electrical stimulati on of CAI outputs. Thus hippocampal interictal activity controls the abilit y of the entorhinal cortex to generate seizures. It also may be proposed th at Schaffer collateral cut may model the epileptic condition in which CA3 d amage results in loss of hippocampal control over the entorhinal cortex. In conclusion, these experiments demonstrate that interictal activity control s rather than promotes ictal events, and functional integrity of CA3 consti tutes a critical control mechanism in temporal lobe epilepsy.