GABAergic mechanisms in absence epilepsy: a computational model of absence epilepsy simulating spike and wave discharges after vigabatrin in WAG/Rij rats.
In this study, the effects of vigabatrin on spike-and-wave discharges (SWDs) were measured in WAG/Rij rats, an animal model of absence epilepsy. Vigabatrin was used with the aim of enhancing GABAergic neurotransmission, and in this way to investigate the role of this process in the properties of SWDs. The study was carried out both in the rat, in vivo, and also using a computational model, in order to test different mechanisms that may account for the changes in SWDs after vigabatrin. The model parameters, representing GABA levels, were changed according to the known, and assumed, mechanism of action of the drug. The results show that the computational model can most adequately simulate the data obtained in vivo on the assumption that the enhancement of GABAergic neurotransmission due to application of vigabatrin is most pronounced at the level of the thalamic relay nuclei (TC cells). Furthermore, vigabatrin was shown to affect both the SWD starting and stopping mechanisms, as reflected by hazard rates. Based on these results, we suggest that GABAergic neurotransmission in TC cells is actively involved in the SWD termination.
Bouwman
Brigitte M
BM
NICI/Department of Biological Psychology, Radboud University Nijmegen, PO Box 9104, 6500 HE Nijmegen, The Netherlands. gittebouwman@zonnet.nl
Suffczynski
Piotr
P
Lopes da Silva
Fernando H
FH
Maris
Eric
E
van Rijn
Clementina M
CM
D000200:Action Potentials / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D030801:Animals, Genetically Modified; D000927:Anticonvulsants / Q000494:pharmacology; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D003198:Computer Simulation; D004195:Disease Models, Animal; D004832:Epilepsy, Absence / Q000188:drug therapy* / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009434:Neural Pathways / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D013788:Thalamus / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D020888:Vigabatrin / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D000927:Anticonvulsants; D005680:gamma-Aminobutyric Acid; D020888:Vigabatrin