EVIDENCE DISPUTING THE LINK BETWEEN SEIZURE ACTIVITY AND HIGH EXTRACELLULAR GLUTAMATE

As seizures in experimental models can be induced by the activation an d suppressed by the inhibition of glutamate receptors, it is often pro posed that a high extracellular glutamate level subsequent to excessiv e presynaptic release and/or altered glutamate uptake is epileptogenic . The purpose of this study was to ascertain the link between seizure activity and high extracellular glutamate, To assist the detection of any putative rise in extracellular glutamate during seizures, microdia lysis was coupled to enzyme-amperometric detection of glutamate, which provides maximal sensitivity and time resolution. Electrical activity and field potential were also recorded through the dialysis membrane to confirm that epileptic activity was present at the sampling site. N o increase in dialysate glutamate content was detected during picrotox in-induced seizures, even when the K+ concentration in the perfusion m edium was raised to 50% above that measured previously during paroxysm al activity. In addition, sustained inhibition of glutamate uptake by L-trans-pyrrolidine-2,4-dicarboxylate increased the extracellular glut amate level >20-fold but did not produce electrophysiological changes indicative of excessive excitation. These findings indicate that seizu res are not necessarily accompanied by an increased extracellular glut amate level and that increased glutamatergic excitation in epilepsy ma y result from other abnormalities such as increased density of glutama te receptors, enhanced activation subsequent to reduced modulation, or sprouting of glutamatergic synapses.