Network hyperexcitability within the deep layers of the pilocarpine-treated rat entorhinal cortex

In this study we report that in the presence of normal buffer, epileptiform dischargesoccur spontaneously (duration=2.60±0.49 s) or can be induced by electrical stimuli(duration=2.50±0.62 s) in the entorhinal cortex (EC) of brain slices obtained frompilocarpine-treated rats but not in those from age-matched, nonepileptic control (NEC)animals. These network-driven epileptiform events consist of field oscillatory sequences atfrequencies greater than 200 Hz that most often initiate in the lateral EC and propagateto the medial EC with 4–63 ms delays. The NMDA receptor antagonist CPP depressesthe rate of occurrence (P <0.01) of these spontaneous epileptiform discharges but failsin blocking them. Paradoxically, stimulus-induced epileptiform responses are enhanced induration during CPP application.However, concomitant application ofNMDAand non-NMDAglutamatergic antagonists abolishes spontaneous and stimulus-induced epileptiform events.Intracellular recordings from lateral EC layer V cells indicate a lower frequency of spontaneoushyperpolarizing postsynaptic potentials in pilocarpine-treated tissue than in NEC (P <0.002)both under control conditions and with glutamatergic receptor blockade; the reversal potentialof pharmacologically isolated GABAA receptor-mediated inhibitory postsynaptic potentialshas similar values in the two types of tissue. Finally, immunohistochemical analysis showsthat parvalbumin-positive interneurons are selectively reduced in number in EC deep layers.Collectively, these results indicate that reduced inhibition within the pilocarpine-treated EClayer V may promote network epileptic hyperexcitability.