308 0090-2977/05/3704-0308 © 2005 Springer Science+Business Media, Inc. Neurophysiology, Vol. 37, No. 4, 2005 A Possible Mechanism of Blocking of Limbic Motor Seizure Reactions Induced by Activation of the Thalamic Reticular Nucleus Z. I. Nanobashvili, 1 T. R. Chachua, 1 I. G. Bilanishvili, 1 G. G. Beradze, 1 T. R. Gotsadze, 1 and N. A. Khizanishvili 1 Neirofiziologiya/Neurophysiology, Vol. 37, No. 4, pp. 352-361, July-August, 2005. Received April 28, 2005. Experiments were directed toward elucidation of the role of the thalamic reticular nucleus (R) in the modulation of generalized seizure reactions under kindling conditions and of the mechanisms mediating the effects of stimulation of the above nucleus on seizure activity. It was shown that activation of the thalamic R in rats limits generalization of the seizure reactions both in the course of development of seizures of limbic genesis (evoked by stimulation of the hippocampus) and under conditions of the existence of a pre-formed epileptic nidus. Tetanic stimulation of the R in cats under conditions of acute experiments induced significant facilitation of IPSPs in thalamo-cortical neurons of the ventrolateral thalamic nucleus. This effect is rather long-lasting and may be considered a mechanism providing blocking of generalized seizures under kindling conditions. Keywords: hippocampus, kindling, seizure activity, reticular nucleus of the thalamus. 1 Beritashvili Institute of Physiology, Academy of Sciences of Georgia, Tbilisi, Georgia. Correspondence should be addressed to Z. I. Nanobashvili (e-mail: besarion@excite.com) and T. P. Chachua (e-mail: tamar1ch@yahoo.com). INTRODUCTION At present, a number of forms of epileptic attacks are intractable (not sensitive to pharmacological treatment) [1, 2]. The search for alternative possibilities for therapy of such disorders motivated ones to study such “antiseizure” approaches as electrical stimulation of afferent nerves and/or profound structures of the brain. Stimulations of the cerebellum [3], locus coeruleus [4, 5], solitary tract nucleus [6], thalamic nuclei [7-9], as well as of the n. vagus [10, 11], were tested as influences potentially capable of blocking seizure attacks in humans and experimentally evoked epileptiform discharges in animals. The results of using such methods were, however, contradictory. This is due to insufficient knowledge of the functional organization of the structures, disorders in which result in the development of epilepsy, and different forms and models of epilepsy used in the above-cited studies. This is why structures whose stimulation is capable of inducing an antiseizure effect by preventing initiation and/or spreading of epileptiform reactions have still not been adequately identified. Kindling is an experimental model allowing experimenters to induce in animals partial seizures with secondary generalization, as well as facilitation of electrographic manifestations (epileptiform discharges) and behavioral seizures induced by repetitive stimulations of a few cerebral structures (mostly structures of the limbic system). Repeated subthreshold stimulation of these cerebral structures results in progressive intensification of seizure activity accompanied by the development of generalized clonico-tonic attacks. An increased excitability of the CNS is preserved for many months and even years in the absence of stimulations, and generalized seizure reactions can be readily provoked within this period by repeated stimulation [12]. At present, the reticular nucleus (R) of the thalamus has attracted special attention among diencephalic structures, which are specially related to the genesis of epilepsy. This nucleus occupies an especially important position between the neocortex and