THALAMIC REGULATION OF EXPERIMENTAL GENERALIZED SEIZURES

实验性全身性癫痫发作的丘脑调节

• 批准号: 3084187
• 负责人: John William Miller
• 金额: $ 7.07万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-08-01 至 1991-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3084187
• 关键词: anticonvulsants; brain mapping; electroencephalography; electrophysiology; generalized seizures; laboratory rat; neural information processing; neural transmission; neurotransmitter metabolism; thalamus

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.

该项目将检验全身性癫痫发作是 由哺乳动物丘脑和意志的特定区域介导 定义这些区域并描述它们的作用。这件事会做到的 通过确定丘脑不连续病变和 微量注射影响主要神经活性物质 阈值上的抑制性或兴奋性神经递质系统 癫痫发作和脑电放电发生的剂量 在抽搐药物的定时持续静脉输注过程中 戊四唑。在丘脑区域的描绘之后 它调节这些癫痫发作，电生理活动 将描述这些地区的特征并将其与 戊四氮期间发生的行为和脑电事件 输液。最后，对各种微量注射的效果进行了比较。 神经递质物质或其激动剂或拮抗剂 丘脑局部电生理活动，皮质 将检查活动、自发行为和癫痫发作。这个 有待研究的化合物将包括作用于受体的试剂 已知在已识别的 丘脑区域和已知具有促惊厥和抗惊厥作用的物质 行为。 阐明丘脑底物不仅调控癫痫发作 将提供对人类基本过程的更好的理解 全身性癫痫，但也会与研究相关 和抗癫痫药物的发展，因为发现了 这些药物的作用部位是了解 他们的机制。