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

Philip De Guzman, Yuji Inaba, Enrica Baldelli, Marco De Curtis, Giuseppe Biagini, Massimo Avoli

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)1867-1883
Number of pages17
JournalJournal of Physiology
Volume586
Issue number7
DOIs
Publication statusPublished - Apr 1 2008

ASJC Scopus subject areas

  • Physiology
  • Medicine(all)

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