Abstracts

RATIONALE: Periodic population bursts in the CA3 area of the hippocampus are an in vitro model of interictal activity. These discharges are thought to be triggered by spontaneous glutamate release at recurrent collateral synapses. Low concentrations of quinoxaline AMPA/kainate receptor antagonists increase the time interval between bursts by diminishing the excitatory effects of the released glutamate. To determine the dose-response relationship between AMPA/kainate antagonism and burst interval, we used the water-soluble, low-affinity glutamate antagonist kynurenic acid (KYNA).
METHODS: Hippocampal coronal slices were prepared from adult (4-6 weeks) Sprague-Dauley rats. A stimulating electrode and an extracellular recording electrode were placed in the stratum pyramidale layer of the CA3. Bursting was induced by a tetanus protocol (100Hz for 1 sec). 100uM picrotoxin blocked GABAA receptors. 10uM glycine was added to the bath to avoid interactions at the glycine site of the NMDA receptor. Evoked responses were established by stimulating for 20usec every 20sec. 20uM KYNA was added to the bath once a baseline response was established.
RESULTS: Following development of spontaneous bursting of the cell body layer of the CA3, addition of 20uM KYNA increases the frequency of interictal events by 25% (n=3). The same concentration of KYNA does not affect the amplitude of evoked responses in this area of the CA3 (n=6).
CONCLUSIONS: Low concentrations of KYNA decreased the interval between bursts. This effect is opposite to previous observations using higher-affinity quinoxaline AMPA/kainate antagonists. Our observations support the hypothesis that low-affinity AMPA/kainate receptor competitive antagonists decrease the post-burst level of receptor desensitization at the glutamatergic synapses that initiate CA3 bursting.
[Supported by: NIH]