The amygdala is a critical brain region for limbic seizure activity, but the mechanisms underlying its epileptic susceptibility are obscure. Several lines of evidence implicate GluR5 (GLU(K5))
kainate receptors, a type of
ionotropic glutamate receptor, in the amygdala's vulnerability to
seizures and epileptogenesis. GluR5
mRNA is abundant in temporal lobe structures including the amygdala. Brain slice recordings indicate that
GluR5 kainate receptors mediate a portion of the synaptic excitation of neurons in the rat basolateral amygdala. Whole-cell voltage-clamp studies demonstrate that
GluR5 kainate receptor-mediated synaptic currents are inwardly rectifying and are likely to be
calcium permeable. Prolonged activation of basolateral amygdala
GluR5 kainate receptors results in enduring synaptic facilitation through a
calcium-dependent process. The selective
GluR5 kainate receptor agonist ATPA induces spontaneous epileptiform bursting that is sensitive to the
GluR5 kainate receptor antagonist
LY293558. Intra-amygdala infusion of ATPA in the rat induces limbic
status epilepticus; in some animals, recurrent spontaneous
seizures occur for months after the ATPA treatment. Together, these observations indicate that
GluR5 kainate receptors have a unique role in triggering epileptiform activity in the amygdala and could participate in long-term plasticity mechanisms that underlie some forms of epileptogenesis. Accordingly,
GluR5 kainate receptors represent a potential target for
antiepileptic and antiepileptogenic
drug treatments. Most
antiepileptic drugs do not act through effects on
glutamate receptors. However,
topiramate at low concentrations causes slow inhibition of
GluR5 kainate receptor-mediated synaptic currents in the basolateral amygdala, indicating that it may protect against
seizures, at least in part, through suppression of
GluR5 kainate receptor responses.