Endogenous and network bursts induced by N-methyl-D-aspartate and magnesium free medium in the CA3 region of the hippocampal slice.
The epileptogenic properties of N-methyl-D-aspartate and magnesium-free medium were investigated in the CA3 region of the hippocampal slice preparation in the rat. Bath application of N-methyl-D-aspartate (5-10 microM) or magnesium-free medium induced both spontaneous and stimulus-evoked bursts. Both endogenous and network bursts were generated, the former always preceding the latter. The paroxysmal depolarizing shift underlying the network bursts generated by N-methyl-D-aspartate and magnesium-free medium resembled a giant excitatory postsynaptic potential with a reversal potential near 0 mV and a synaptic input in the apical dendrites above the mossy fibre zone. In the presence of N-methyl-D-aspartate or magnesium-free medium, population bursts were synchronized by activating single CA3 neurons. N-methyl-D-aspartate receptor antagonists prevented the development of N-methyl-D-aspartate-induced spontaneous and stimulus-evoked bursts. However, the only N-methyl-D-aspartate receptor antagonist effective in preventing such bursts in magnesium-free medium was DL-3-[(+/-)-2-carboxypiperazin-4-yl-]-propyl-1-phosphonic acid. Endogenous bursting in the CA3 region has not been observed with other convulsants and thus may reflect the novel voltage dependence of the N-methyl-D-aspartate receptor gated ionic channel. N-methyl-D-aspartate receptors may also partially contribute to the excitatory interaction between CA3 neurons and thereby account for the synchronization of the population observed when activating single CA3 neurons.
Neuman
R S
RS
INSERM Unite 29, Hôpital de Port-Royal, Paris, France.
Cherubini
E
E
Ben-Ari
Y
Y
D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D003470:Culture Media; D003712:Dendrites / Q000648:ultrastructure; D004594:Electrophysiology; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D066298:In Vitro Techniques; D008274:Magnesium / Q000494:pharmacology*; D016202:N-Methylaspartate; D009415:Nerve Net / Q000187:drug effects* / Q000502:physiology; D009420:Nervous System / Q000187:drug effects*; D009474:Neurons / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D003470:Culture Media; D001224:Aspartic Acid; D016202:N-Methylaspartate; D008274:Magnesium