Plasticity of AMPA and NMDA receptor-mediated epileptiform activity in a chronic model of temporal lobe epilepsy.
We have investigated the consequences of tetanic stimulation on epileptiform activity mediated by NMDA and AMPA receptors in an experimental model of human temporal lobe epilepsy. Recordings were performed in the CA1 area of the hippocampus one week following intracerebroventricular injection of kainic acid. Data presented here show that, after tetanic stimulation, there was a long-term increase in the amplitude of the population spikes associated with the epileptiform burst. This activity was triggered by the simultaneous activation of both NMDA and AMPA receptors. However, whilst the pharmacologically isolated AMPA component of this burst underwent long-term enhancement, the NMDA component underwent a long-term decrease in amplitude. These data suggest that in this chronic model of epileptiform activity, there is long-term potentiation of excitatory mediated events regulated primarily by AMPA receptors. Furthermore, the slow time course of the NMDA receptor-mediated synaptic conductances was responsible for prolonging the duration of the epileptiform bursts. However, the powerful depression of NMDA receptor-mediated events following tetanic stimulation suppressed the normally large potentiation of the overall response. Thus although it has been suggested that the NMDA receptor-mediated synaptic events contribute to the epileptogenic properties of the neocortex and hippocampus, this evoked depression may act as an intrinsic anticonvulsant mechanism.
Bernard
C
C
Department of Physiology and Pharmacology, University of Southampton, UK.
Wheal
H V
HV
D000818:Animals; D002908:Chronic Disease; D004195:Disease Models, Animal; D004558:Electric Stimulation; D004833:Epilepsy, Temporal Lobe / Q000503:physiopathology*; D006624:Hippocampus / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D007608:Kainic Acid; D017774:Long-Term Potentiation; D008297:Male; D009473:Neuronal Plasticity / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D013746:Tetany
D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D007608:Kainic Acid