Epileptiform activity but not synaptic plasticity is blocked by oxidation of NMDA receptors in a chronic model of temporal lobe epilepsy.
Simultaneous extracellular recordings were performed in stratum radiatum and stratum pyramidale of hippocampal slices 7 days following unilateral intracerebroventricular injections of kainic acid. In this ex vivo experimental model of human temporal lobe epilepsy, stimulation of the surviving commissural fibres in stratum radiatum produced graded epileptiform activity in the CA1 area. The oxidizing reagent 5,5'-dithiobis (2-nitrobenzoic acid) (DTNB) acting at NMDA receptors redox sites decreases NMDA receptor-mediated responses by half and suppresses evoked epileptiform discharges. We have examined the effect of DTNB on NMDA-dependent bidirectional synaptic plasticity and EPSP/spike coupling. DTNB treatment did not prevent either long-term potentiation induced by tetanic stimulation or long-term depression induced by low frequency stimulation of field EPSPs. Application of DTNB alone did not induce EPSP/spike dissociation. However, both high and low frequency stimulations induced EPSP/spike potentiation indicating that neurons had a high probability to discharge in synchrony. These results suggest that oxidizing reagents may provide novel antiepileptic treatments since they decrease NMDA-dependent evoked epileptiform activity but do not interfere with either NMDA-dependent synaptic plasticity or the probability of synchronous discharge.
Quesada
O
O
INSERM U29, Hôpital de Port Royal, Paris, France.
Hirsch
J C
JC
Gozlan
H
H
Ben-Ari
Y
Y
Bernard
C
C
D000818:Animals; D004195:Disease Models, Animal; D004228:Dithionitrobenzoic Acid / Q000494:pharmacology*; D004833:Epilepsy, Temporal Lobe / Q000378:metabolism*; D008297:Male; D009473:Neuronal Plasticity / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects*; D013997:Time Factors
D016194:Receptors, N-Methyl-D-Aspartate; D004228:Dithionitrobenzoic Acid