ENHANCED PROPAGATION OF EPILEPTIFORM ACTIVITY THROUGH THE KINDLED DENTATE GYRUS

Extracellular recordings were performed in combined hippocampal-entorh inal cortex (HC-EC) slices obtained from control and commissural kindl ed rats to investigate the propagation of epileptiform activity from t he entorhinal cortex (EC) to the hippocampus (HC) after chronic epilep sy. Lowering extracellular Mg2+ concentration in control slices induce d epileptiform activity consisting of spontaneous epileptiform bursts in area CA3 and of electrographic seizures in the EC. In contrast, the CA3 region of HC-EC slices obtained from kindled rats displayed signi ficantly longer lasting epileptiform bursts and electrographic seizure s. The electrographic seizures that were absent in controls propagated from the EC because disconnecting the HC from the EC stopped their oc currence in the CA3, whereas epileptiform bursts persisted with an una ltered pattern and frequency. Thus the area CA3 is affected by kindlin g and contributes to the spread of epileptiform activity within the EC -HC complex. We developed a method to induce focal epileptiform activi ty in the EC by locally perfusing the gamma-aminobutyric acid-A (GABA) antagonist bicuculline (50 mM) in 10 mM KCl containing artificial cer ebrospinal fluid. This method enabled us to investigate the propagatio n of epileptiform discharges from the disinhibited EC to the DG withou t affecting the DG with the epileptogenic medium. We show here that ki ndling facilitates the propagation of epileptiform activity through th e DG. These data are consistent with the normal function of the DG as a filter limiting the spread of epileptiform activity within the HC-EC complex. This gating mechanism breaks down after chronic epilepsy ind uced by kindling.