Synaptic modifications accompanying epileptogenesis in vitro: long-term depression of GABA-mediated inhibition.
We used an in vitro model similar to kindling to examine the processes underlying epileptogenesis. A 60 Hz train was applied every 5-10 min to the Schaffer collateral pathways in guinea pig hippocampal slices until epileptiform bursting was elicited in the CA3 region. The resultant alterations in both spontaneous and evoked activities were studied using intracellular recordings from CA3 pyramidal cells. An attempt was made to elucidate the synaptic modifications responsible for the conversion to this state of enhanced excitability. Analyses revealed that the emergence of epileptiform discharge was accompanied by a long-term depression of evoked inhibitory conductances. This tetanus-induced reduction of inhibition involved both the early and late phases of the evoked hyperpolarization, suggesting modification of both the GABAA and GABAB receptor-mediated events. Previous studies have suggested that NMDA receptor activation plays an important role in the induction of epileptiform activity in this model. Our data, showing that depression of inhibition can be induced in the presence of CNQX, is consistent with this hypothesis. The parallel development of long-term depression of inhibition and epileptiform bursting following tetanic stimulation suggests that plasticity of the inhibitory transmission process is a potential source of vulnerability contributing to epileptogenesis.
Merlin
L R
LR
Department of Neurology, State University of New York Health Science Center, Brooklyn 11203.
Wong
R K
RK
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D000200:Action Potentials / Q000502:physiology; D000818:Animals; D004558:Electric Stimulation; D004827:Epilepsy / Q000503:physiopathology*; D006168:Guinea Pigs; D006624:Hippocampus / Q000503:physiopathology*; D066298:In Vitro Techniques; D017966:Pyramidal Cells / Q000502:physiology; D011810:Quinoxalines / Q000494:pharmacology; D013569:Synapses / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects; D013746:Tetany / Q000503:physiopathology; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D011810:Quinoxalines; D005680:gamma-Aminobutyric Acid; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione