Abstracts

Activation of kainate receptors (KARs) has been shown to modulate excitatory and inhibitory synaptic transmission. Kainate has a dose-dependent biphasic effect on excitatory postsynaptic currents (EPSCs) in hippocampus. Although kainate receptors are expressed in the prefrontal cortex, the effects of kainate on EPSCs in layer II/III pyramidal cells have not been studied. In addition, the role of presynaptic KARs in modulation of epileptiform activity has not been examined. This study has examined the effect of bath application of kainate on EPSCs, mEPSC, and epileptiform discharges in neocortex. Neocortical brain slices were prepared from rats 18-23 days of age. Whole cell patch clamp recordings were obtained from layer II/III of prefrontal cortex. EPSCs were evoked by subthreshold stimulation in deeper cortical layers in the presence of bath-applied bicuculline. Epileptiform discharges were evoked by stronger stimulation. mEPSCs were recorded in presence of TTX. Kainate (50 nM - 3 [micro]M) was bath applied. In the presence of bicuculline, low concentrations of KA (50 [ndash] 500 nM) increased the amplitude of evoked EPSCs, while higher concentration (1 [ndash] 3 [micro]M) cause a depression. Kainate had a biphasic effect on the probability of evoking epileptiform discharges, causing an increase at lower concentration and a decrease at higher concentration. At 250 and 500 nM, kainate application increased the amplitude and area of epileptiform discharges. Application of kainate at a higher concentration (3[micro]M) caused a transient increase in both the amplitude and response area of epileptiform discharges followed by a sustained decrease below control levels. Miniature EPSC frequency but not amplitude was also increased by kainate (250 nM). Our results show that presynaptic facilitatory KARs are present on layer II/III pyramidal cells where they modulate excitatory transmission and epileptiform discharges in a dose-dependent manner. Activation of these receptors by synaptically released glutamate is proconvulsant and may underlie the convulsant action of kainate. (Supported by NS22373)