Enhanced propagation of epileptiform activity through the kindled dentate gyrus.
Extracellular recordings were performed in combined hippocampal-entorhinal cortex (HC-EC) slices obtained from control and commissural kindled rats to investigate the propagation of epileptiform activity from the entorhinal cortex (EC) to the hippocampus (HC) after chronic epilepsy. Lowering extracellular Mg2+ concentration in control slices induced 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 significantly longer lasting epileptiform bursts and electrographic seizures. The electrographic seizures that were absent in controls propagated from the EC because disconnecting the HC from the EC stopped their occurrence in the CA3, whereas epileptiform bursts persisted with an unaltered pattern and frequency. Thus the area CA3 is affected by kindling and contributes to the spread of epileptiform activity within the EC-HC complex. We developed a method to induce focal epileptiform activity in the EC by locally perfusing the gamma-aminobutyric acid-A (GABA) antagonist bicuculline (50 mM) in 10 mM KCl containing artificial cerebrospinal fluid. This method enabled us to investigate the propagation of epileptiform discharges from the disinhibited EC to the DG without affecting the DG with the epileptogenic medium. We show here that kindling facilitates the propagation of epileptiform activity through the 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 induced by kindling.
Behr
J
J
Department of Neurology, Reed Neurological Research Center, UCLA School of Medicine, Los Angeles, California 90095-1769, USA.
Lyson
K J
KJ
Mody
I
I
D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D002908:Chronic Disease; D018891:Dentate Gyrus / Q000503:physiopathology*; D018728:Entorhinal Cortex / Q000503:physiopathology*; D004827:Epilepsy / Q000503:physiopathology*; D005071:Evoked Potentials / Q000187:drug effects; D018756:GABA Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D007696:Kindling, Neurologic / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar
D018756:GABA Antagonists; D001640:Bicuculline