Kainate receptor-dependent axonal depolarization and action potential initiation in interneurons.

Kainate receptor agonists are powerful chemoconvulsants and excitotoxins. These properties are in part explained by depolarization of hippocampal principal neurons. However, kainate also depresses evoked inhibitory signals in pyramidal neurons, and promotes spontaneous GABA release from interneurons. The mechanisms underlying these phenomena are not fully understood, nor are the consequences for the inhibitory traffic among interneurons. We report that both the amplitude and the frequency of spontaneous IPSCs recorded in interneurons were enhanced by low concentrations of kainate, but action potential-independent IPSCs were unaffected. In the presence of GABA(A) receptor antagonists, kainate lowered the threshold for antidromic action potential generation, suggesting that interneuron axons are directly depolarized; this effect was mimicked by synaptically released glutamate. Kainate application also induced spontaneous antidromic action potentials. Axonal receptors are thus important in initiating the intense interneuronal activity triggered by kainate, which in turn influences inhibitory signaling to principal cells.