Changes in mIPSCs and sIPSCs after kainate treatment: possible actions mediated by the direct activation of kainate receptors.

Changes in mIPSCs and sIPSCs after kainate treatment: possible actions mediated by the direct activation of kainate receptors To the Editor: In a very interesting paper, Shao and Dudek (2005) described the changes in miniature inhibitory postsyn-aptic currents (mIPSCs) and spontaneous inhibitory synaptic currents (sIPSCs) that occur after kainate treatment recorded in hippocampal dentate granule cells. Basically, in acutely and chronically treated rats, the authors observed a 30% decrease in the frequency of mIPSCs that did not recover over a prolonged period of time, whereas the sIPSC frequency of action-potential dependent events remained unaffected. In contrast to the diminution of mIPSC frequency, which is indicative of a presynaptic events reducing quantal release, if anything, the authors observed an increase in the mIPSC amplitudes reporting changes in postsynaptic parameters. The primary observation of a decrease in the mIPSC frequency was interpreted by the authors as being due to a decrease in the number of presynaptic interneurons, this perhaps being compensated for in situ by increased firing of the surviving interneurons. Notwithstanding this conclusion purporting interneuron loss, alternative explanations of the reported effect of kainate are equally tenable. The notable fact that there is a 30% decrease of mIPSC frequency after kainate reported by Shao and Dudek (2005) is indeed reminiscent of results obtained previously by direct activation of presynaptic kainate receptors (KARs) in slices from the CA1 region of the rat hippocampus (Cossart et al. There the interpretation of the data was that a decrease of mIPSC is effectively mediated by the activation of KARs situated in the inhibitory terminals. Accordingly, as pointed out by Echegoyen and Soltesz (2005), a decrease in the probability of GABA release provides a plausible alternatively explanation for the decrease on mIPSC frequency observed by Shao and Dudek (2005). The question is whether it is possible that the activation of KARs receptors, classically considered to be ionotropic, can produce a long-lasting effect on GABA release by changing the probability of release. Arguing against an ionotropic effect of KARs in this context, Rodríguez-Moreno and Lerma (1998) and Rodríguez-Moreno et al. (2000) have found that KARs can act via a novel metabotropic mechanism. In fact, the inhibition of GABA release at hippocampal inhibitory interneurons could be described as overtly metabotropic given that it was supported by the activation of a G i/o protein and a phospholipase C (PLC)/protein kinase C (PKC) pathway. In light of these observations, the …