In this study we report that in the presence of normal buffer, epileptiform discharges occur 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 from pilocarpine-treated rats but not in those from age-matched, nonepileptic control (NEC) animals. These network-driven epileptiform events consist of field oscillatory sequences at frequencies greater than 200 Hz that most often initiate in the lateral EC and propagate to the medial EC with 4-63 ms delays. The NMDA receptor antagonist CPP depresses the rate of occurrence (P < 0.01) of these spontaneous epileptiform discharges but fails in blocking them. Paradoxically, stimulus-induced epileptiform responses are enhanced in duration during CPP application. However, concomitant application of NMDA and non-NMDA glutamatergic antagonists abolishes spontaneous and stimulus-induced epileptiform events. Intracellular recordings from lateral EC layer V cells indicate a lower frequency of spontaneous hyperpolarizing postsynaptic potentials in pilocarpine-treated tissue than in NEC (P < 0.002) both under control conditions and with glutamatergic receptor blockade; the reversal potential of pharmacologically isolated GABA(A) receptor-mediated inhibitory postsynaptic potentials has similar values in the two types of tissue. Finally, immunohistochemical analysis shows that parvalbumin-positive interneurons are selectively reduced in number in EC deep layers. Collectively, these results indicate that reduced inhibition within the pilocarpine-treated EC layer V may promote network epileptic hyperexcitability.
Network hyperexcitability within the deep layers of the pilocarpine-treated rat entorhinal cortex / P., De Guzman; Y., Inaba; E., Baldelli; M., De Curtis; G., Biagini; Avoli, Massimo. - In: THE JOURNAL OF PHYSIOLOGY. - ISSN 0022-3751. - STAMPA. - 586:7(2008), pp. 1867-1883. [10.1113/jphysiol.2007.146159]
Network hyperexcitability within the deep layers of the pilocarpine-treated rat entorhinal cortex
AVOLI, Massimo
2008
Abstract
In this study we report that in the presence of normal buffer, epileptiform discharges occur 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 from pilocarpine-treated rats but not in those from age-matched, nonepileptic control (NEC) animals. These network-driven epileptiform events consist of field oscillatory sequences at frequencies greater than 200 Hz that most often initiate in the lateral EC and propagate to the medial EC with 4-63 ms delays. The NMDA receptor antagonist CPP depresses the rate of occurrence (P < 0.01) of these spontaneous epileptiform discharges but fails in blocking them. Paradoxically, stimulus-induced epileptiform responses are enhanced in duration during CPP application. However, concomitant application of NMDA and non-NMDA glutamatergic antagonists abolishes spontaneous and stimulus-induced epileptiform events. Intracellular recordings from lateral EC layer V cells indicate a lower frequency of spontaneous hyperpolarizing postsynaptic potentials in pilocarpine-treated tissue than in NEC (P < 0.002) both under control conditions and with glutamatergic receptor blockade; the reversal potential of pharmacologically isolated GABA(A) receptor-mediated inhibitory postsynaptic potentials has similar values in the two types of tissue. Finally, immunohistochemical analysis shows that parvalbumin-positive interneurons are selectively reduced in number in EC deep layers. Collectively, these results indicate that reduced inhibition within the pilocarpine-treated EC layer V may promote network epileptic hyperexcitability.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.