Synaptic plasticity in the pathway from the medial geniculate body to the lateral amygdala is induced by seizure repetition

Abstract

Repeated induction of generalized audiogenic seizures (AGS) (AGS kindling) induces expansion of the seizure network and evokes additional convulsive behaviors. The medial geniculate body (MGB) and amygdala are implicated in the network expansion induced by AGS kindling, although these sites are not required for AGS before kindling. A recent study indicated that amygdala neuronal responses are greatly increased by AGS kindling. The present study examined the effects of AGS kindling on the thalamo–amygdala pathway in genetically epilepsy-prone rats (GEPR-9s) by examining the neuronal responses in lateral amygdala (LAMG) to electrical stimulation in MGB in vivo. AGS kindling in GEPR-9s involved 14 AGS in response to twice daily acoustic stimulation. Sham-kindled normals received the mean stimulation parameters presented to kindled animals. Spontaneous LAMG extracellular action potentials (APs) and APs evoked by electrical stimuli in the MGB were examined in ketamine-anesthetized rats. The mean spontaneous LAMG firing in kindled GEPR-9s was significantly elevated as compared to non-kindled GEPRs, sham-kindled and non-kindled normals. LAMG firing evoked by MGB stimuli in kindled GEPR-9s was significantly elevated, and a significant mean threshold reduction was also observed in kindled GEPR-9s, as compared to other animal groups. These changes may be due to enhanced glutamate receptor-mediated excitation and/or compromised GABA receptor-mediated inhibition in AMG, as previously reported in electrical kindling in the amygdala. These findings indicate that AGS kindling increases the efficacy of the thalamo–amygdala pathway in GEPR-9s, suggesting that synaptic plasticity in this portion of the expanded neuronal network is an important pathophysiological mechanism subserving AGS kindling.