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Network hyperexcitability within the deep layers of the pilocarpine‐treated rat entorhinal cortex
Author(s) -
De Guzman Philip,
Inaba Yuji,
Baldelli Enrica,
De Curtis Marco,
Biagini Giuseppe,
Avoli Massimo
Publication year - 2008
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2007.146159
Subject(s) - pilocarpine , entorhinal cortex , inhibitory postsynaptic potential , postsynaptic potential , neuroscience , nmda receptor , glutamatergic , chemistry , excitatory postsynaptic potential , stimulus (psychology) , medicine , endocrinology , receptor , hippocampus , glutamate receptor , biology , epilepsy , psychology , biochemistry , psychotherapist
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.