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 language | English |
|---|---|
| Pages (from-to) | 1867-1883 |
| Number of pages | 17 |
| Journal | Journal of Physiology |
| Volume | 586 |
| Issue number | 7 |
| DOIs | |
| Publication status | Published - Apr 1 2008 |
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ASJC Scopus subject areas
- Physiology
- Medicine(all)
Cite this
Network hyperexcitability within the deep layers of the pilocarpine-treated rat entorhinal cortex. / De Guzman, Philip; Inaba, Yuji; Baldelli, Enrica; De Curtis, Marco; Biagini, Giuseppe; Avoli, Massimo.
In: Journal of Physiology, Vol. 586, No. 7, 01.04.2008, p. 1867-1883.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Network hyperexcitability within the deep layers of the pilocarpine-treated rat entorhinal cortex
AU - De Guzman, Philip
AU - Inaba, Yuji
AU - Baldelli, Enrica
AU - De Curtis, Marco
AU - Biagini, Giuseppe
AU - Avoli, Massimo
PY - 2008/4/1
Y1 - 2008/4/1
N2 - 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.
AB - 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.
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U2 - 10.1113/jphysiol.2007.146159
DO - 10.1113/jphysiol.2007.146159
M3 - Article
VL - 586
SP - 1867
EP - 1883
JO - Journal of Physiology
JF - Journal of Physiology
SN - 0022-3751
IS - 7
ER -