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 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.
de Guzman
Philip
P
Montreal Neurological Institute and Department of Neurology & Neurosurgery, McGill University, Montreal, QC H3A 2B4, Canada.
Inaba
Yuji
Y
Baldelli
Enrica
E
de Curtis
Marco
M
Biagini
Giuseppe
G
Avoli
Massimo
M
D000200:Action Potentials / Q000502:physiology; D000818:Animals; D004195:Disease Models, Animal; D004558:Electric Stimulation; D018728:Entorhinal Cortex / Q000187:drug effects / Q000503:physiopathology*; D004827:Epilepsy / Q000503:physiopathology*; D008297:Male; D018721:Muscarinic Agonists / Q000494:pharmacology*; D009415:Nerve Net / Q000187:drug effects / Q000503:physiopathology*; D009474:Neurons / Q000502:physiology; D010862:Pilocarpine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018079:Receptors, GABA / Q000187:drug effects / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000502:physiology
D018721:Muscarinic Agonists; D018079:Receptors, GABA; D016194:Receptors, N-Methyl-D-Aspartate; D010862:Pilocarpine