THALAMIC REGULATION OF EXPERIMENTAL GENERALIZED SEIZURES

该项目将测试全身性癫痫发作是 由哺乳动物丘脑的特定区域介导， 界定这些区域并说明其作用。 为此将 通过确定离散丘脑病变的影响， 微量注射影响主要神经活性物质 抑制性或兴奋性神经递质系统的阈值 癫痫发作和脑电图放电的剂量 在定时连续静脉输注惊厥药物期间 戊四氮 根据丘脑区域的划分 控制癫痫发作的神经系统， 这些地区的特点和相关性， 戊四氮注射过程中发生的行为和脑电图事件 输液 最后，研究了显微注射不同浓度的 神经递质物质或其激动剂或拮抗剂， 局部丘脑皮层电生理活动 将检查活动、自发行为和癫痫发作。 的 待研究的化合物将包括作用于受体的药剂 已知在已鉴定的 丘脑区域和已知促惊厥和抗惊厥物质 行动 阐明调节癫痫发作的丘脑底物不仅 将提供更好的理解人类的基本过程， 全身性癫痫，但也将有相关的研究 和抗癫痫药物的发展，因为确定了 这些药物的作用部位是了解 他们的机制。

This project will test the hypothesis that generalized seizures are mediated by specific regions of the mammalian thalamus and will define such regions and characterize their role. This will be done by determining the effects of discrete thalamic lesions and microinjection of neuroactive substances which affect major inhibitory or excitatory neurotransmitter systems on the threshold doses for seizures and electroencephalographic discharges occurring during timed continuous intravenous infusion of the convulsant drug pentylenetetrazol. Following the delineation of the thalamic areas which regulate these seizures, the electrophysiological activity of these regions will be characterized and correlated with the behavioral and EEG events occurring during pentylenetetrazol infusion. Finally, the effects of microinjection of a variety of neurotransmitter substances or their agonist or antagonists on local thalamic electrophysiological activity, electrocortical activity, spontaneous behavior and seizures will be examined. The compounds to be studies will include agents acting on receptors known to be present in high concentrations in the identified thalamic regions and substances with known pro- and anticonvulsant actions. Elucidating the thalamic substrate regulating seizures not only would provide greater understanding of the basic processes of human generalized epilepsy, but also would have relevance to the study and development of antiepileptic drugs, since identification of the site of action of these drugs is a prerequisite for understanding their mechanism.