INVOLVEMENT OF NIGRAL GLUTAMATERGIC INPUTS IN THE CONTROL OF SEIZURESIN A GENETIC MODEL OF ABSENCE EPILEPSY IN THE RAT

The reticular part of the substantia nigra is known to be a critical s ite in the control of epileptic seizures. Potentiation of the direct s triatonigral GABAergic projection has been shown to suppress seizures in different animal models of epilepsy. Besides this GABAergic input, the substantia nigra receives glutamatergic inputs, especially from th e indirect striatonigral pathway, via the subthalamic nucleus. To inve stigate the involvement of the nigral excitatory amino acid transmissi on in the remote control of non-convulsive generalized seizures, sever al drugs interacting with glutamatergic receptors were first injected into the substantia nigra pars reticulata in rats with spontaneous abs ence seizures. Blockade of N-methyl-D-aspartate receptors suppressed s pontaneous generalized non-convulsive seizures in the rat, whereas blo ckade of non-N-methyl-D-aspartate receptors was without effect. Second , inhibition of the subthalamic projection by bilateral injections of a GABAergic agonist in this structure similarly suppressed absence sei zures. These results suggest that excitatory amino acid inputs are cri tical in the triggering of the nigral control of generalized epilepsie s. Furthermore, they support the hypothesis of a possible involvement of the subthalamonigral pathway in the control of generalized non-conv ulsive seizures.