29,30 These EPSCs differ from AMPA receptor-mediated EPSCs by their longer kinetics and their smaller amplitude. In addition, mixed AMPA/kainate receptor-mediated EPSCs are also recorded, indicating that both receptor types are involved in mediating fast glutamatergic synaptic activity. Kainate receptors are also enriched on GABAergic interneurons, Inhibitors,research,lifescience,medical where they provide almost half the ongoing glutamatergic activity.29,31 A direct association
between mossy fiber terminals and “kainatergic” synapses has also been shown, confirming the close relationship between kainate signaling and the CA3 mossy fiber terminals.29 Kainatergic postsynaptic currents (PSCs) have a slower and smaller amplitude than the conventional AMPA receptor-mediated currents, suggesting that they will play different tunes in the generation of synchronized oscillations. Several subclasses of kainate receptors have been cloned, including the GluR5 subunits that are enriched on interneurons, and the GluR 6 subunits enriched on mossy fiber synapses.32-34 The Inhibitors,research,lifescience,medical GluR 6 subunits are enriched on mossy fiber terminals, and have been associated with seizures. The threshold for seizure Inhibitors,research,lifescience,medical generation is reduced
in transgenic animals depleted of this subunit.17,35,36 On the other hand, GluR 5 subunits are enriched on selleck products interneurons where they provide as much as half of the excitatory inputs.17,37 Inhibitors,research,lifescience,medical Therefore, kainate signaling will both facilitate paroxysmal activity by means of GluR 6 receptor-containing synapses, and prevent seizures by means of GluR 5 receptor-containing synapses and the augmented inhibition that they produce.31,38 The kainate animal model generates a seizu d brain damage syndrome that mimi man temporal lobe epilepsies Systemic or intracerebral injections of kainate generate long-lasting limbic seizures, followed by a pattern of lesions Inhibitors,research,lifescience,medical in the hippocampus and other limbic structures.17,27,39,40 The clectrographic pattern and the subsequent lesions have a distribution that
is quite similar to that observed in patients suffering from temporal lobe epilepsy (TLE) with Methisazone a preferential involvement of the CA3 and CA1regions, GABAergic interneurons, and the pyriform cortex, as well as other limbic cortices and subcortical regions. The amygdala plays a central role in the sequence, as suggested by the powerful actions of very low concentrations of kainate injected in that region and the clinical and electrographic signs that imply the involvement of that structure. Extensive investigations clearly indicate that the neuronal cell loss is at least in part due to the excessive activation of certain glutamatergic fibers, and in particular the mossy fiber terminals that produce a lesion of the neurons that they innervate. From cell loss to neosynapse formation Neurons adjacent to, or even linked to, damaged neurons do not remain idle.