EFFECTS OF GLUTAMATE APPLICATION ON THE RHYTHM OF LOW MAGNESIUM-INDUCED EPILEPTIFORM ACTIVITY IN HIPPOCAMPAL SLICES OF GUINEA-PIGS

The extracellular concentration of glutamate has previously been repor ted to increase to more than 10-fold the basal level during seizure ac tivity. In the present study, we tested whether localized increases in extracellular glutamate concentration influence the rhythm of epilept iform discharges in the low-magnesium epilepsy model. In hippocampal s lices of guinea-pigs, epileptiform activity was induced by omission of magnesium from the bath fluid. Glutamate and its subreceptor, agonist s N-methyl-D-aspartate (NMDA) and lpha-amino-3-hydroxy-5-methyl-4-isox azolepropionic acid (AMPA) were ejected into different strata of the C A3 and CA1 regions using microiontophoretic and micropressure applicat ion. Glutamate, NMDA and AMPA applied to the CA3 region, but not to th e CA1 region, induced a short-lasting increase in epileptiform dischar ge frequency, often followed by a transient reduction. The effect was most pronounced with application into the stratum lacunosum-moleculare of the CA3 region and could only be evoked in slices exceeding 400 mu m in thickness. The effects on the rhythm of epileptiform discharges induced by NMDA and AMPA were blocked by their specific receptor antag onists. They were not influenced by application of GABA(A) and GABA(B) receptor antagonists. Changes in somatic membrane potential of CA3 py ramidal neurons did not correlate with changes in the rhythm of epilep tiform discharges elicited in this region. The transient suppression o f epileptiform discharges that followed the increase in discharge freq uency was abolished by an adenosine A(1) receptor antagonist. We propo se that localized increases in extracellular glutamate concentration m odify the rhythm of epileptiform discharges due to changes in neuronal network activity.