Abstracts

RATIONALE: Application of 4-aminopyridine (4AP) to combined hippocampus-entorhinal cortex (EC) slices obtained from control mice induces ictal epileptiform discharges that originate in EC and disappear over time, as well as brief interictal discharges that initiate in the CA3 subfield and occur throughout the experiment (Barbarosie and Avoli, J Neurosci 17:9308-14, 1997). CA3-driven interictal discharges may control EC epileptogenicity since cutting the Schaffer collaterals, which prevents hippocampal output activity to enter the EC, uncovers ictal activity in slices in which ictal discharges had disappeared. Pilocarpine injection in vivo causes CA3 cell loss and the appearance of recurrent limbic seizures. Hence it may be hypothesized that slices obtained from pilocarpine-treated mice should respond differently to 4AP as compared with control slices. METHODS: Procedures for obtaining and maintaining combined slices, as well as electrophysiological recordings were performed as previously reported (Barbarosie and Avoli, 1997). Pilocarpine treatment (i.p. injection of 300mg/Kg) was carried out 14-24 days before slicing. RESULTS: Slices obtained from control mice responded to 4AP (50 M) by generating CA3-driven interictal discharges (duration=150-300ms; frequency=0.8-1.1Hz) along with ictal discharges of EC origin (duration?15s) that disappeared over time. By contrast 4AP application to slices obtained from pilocarpine-treated mice disclosed less frequent (0.5-0.7Hz) and longer (180-400ms) interictal discharges along with ictal discharges that persisted throughout the experiment (up to 5 hours). CONCLUSIONS: Our results indicate that pilocarpine-treated mouse hippocampus-EC slices are characterized by different network interactions when compared with control animals. We propose that CA3 damage leads to a loss of control onto the EC, which allows EC to generate ictal discharges.