THE ROLE OF BASAL GANGLIA IN THE CONTROL OF GENERALIZED ABSENCE SEIZURES

During the last two decades, evidence has accumulated to demonstrate t he existence, in the central nervous system, of an endogenous mechanis m that exerts an inhibitory control over different forms of epileptic seizures. The substantia nigra and the superior colliculus have been d escribed as key structures in this control circuit; inhibition of GABA ergic neurons of the substantia nigra pars reticulata results in suppr ession of seizures in various animal models of epilepsy. The role in t his control mechanism of the direct GABAergic projection from the stri atum to the substantia nigra and of the indirect pathway, from the str iatum through the globus pallidus and the subthalamic nucleus, was exa mined in a genetic model of absence seizures in the rat. In this model , pharmacological manipulations of both the direct and indirect pathwa ys resulted in modulation of absence seizures. Activation of the direc t pathway or inhibition of the indirect pathway suppressed absence sei zures through disinhibition of neurons in the deep and intermediate la yers of the superior colliculus. Dopamine D1 and D2 receptors in the n ucleus accumbens, appear to be critical in these suppressive effects. Along with data from the literature, our results suggest that basal ga nglia circuits play a major role in the modulation of absence seizures and provide a framework to understand the role of these circuits in t he modulation of generalized seizures. (C) 1998 Elsevier Science B.V. All rights reserved.