EPILEPSY RESEARCH CENTER

癫痫研究中心

• 批准号: 3099369
• 负责人: PETER A KELLAWAY
• 金额: $ 41.77万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 1978
• 资助国家: 美国
• 起止时间: 1978-06-01 至 1997-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3099369
• 关键词: brain electrical activity; developmental neurobiology; epilepsy

This multidisciplinary research program combines various analytic techniques to investigate the synaptic physiology, biophysics, and biochemistry of epileptogenesis and the development of the epileptic process in mammalian brain. The goal is to apply new methods of selectively measuring excitability changes at excitatory synapses, second-messenger modulation of inhibitory synaptic transmission, and axonal sprouting in specific neural networks to determine whether key excitability defects in epileptic brain are mediated by use-dependent and potentially reversible mechanisms. The research tests specific hypotheses extending from the molecular to the structural levels of neural organization, and is based on three model systems. (1) Acute epileptogenesis, using hippocampal slice techniques, will be studied with a focus on the immediate role of use-dependent plastic properties of recurrent excitatory synapses in the CA3 subfield and on long-term potentiation in the generation of epileptiform activity. (2) Chronic focal epileptogenesis, using slices from kindled animals, will be studied to determine the functional consequences of aberrant mossy fiber growth during prolonged abnormal stimulation. (3) Inherited generalized epileptogenesis, using slices from epileptic mice with single-locus genetic mutations, will be studied to examine synaptic and biochemical mechanisms underlying network bursting, modulation of GABA- receptor-mediated inhibition, and aberrant axonal sprouting and neosynaptogenesis. A critical element of this research program is the high degree of interaction and collaboration, at both technical and conceptual levels, among the scientists who comprise the research team.

这一多学科研究计划结合了各种分析 研究突触生理学、生物物理学和 癫痫的生物化学与癫痫的发生发展 哺乳动物大脑中的过程。我们的目标是应用新的方法 选择性地测量兴奋性突触的兴奋性变化， 抑制性突触传递的第二信使调制，以及 轴突萌发在特定神经网络中的关键 癫痫脑内兴奋性缺陷是由使用依赖和 潜在的可逆机制。 这项研究测试了特定的假设，从分子到 神经组织的结构层次，并基于三个模型 系统。(1)采用海马区切片技术的急性癫痫发生； 将重点研究依赖使用的直接作用 CA3亚区复发性兴奋性突触的可塑性 以及长时程增强在癫痫样活动产生中的作用。 (2)慢性局灶性癫痫发作，使用点燃动物的切片， 将进行研究以确定异常的功能后果 在长时间的异常刺激下，苔藓纤维生长。(3)继承 使用癫痫小鼠的切片研究全面性癫痫的发生 单基因座基因突变，将被研究以检查突触和 网络爆裂的生化机制，GABA的调制- 受体介导的抑制和异常轴突萌发 新突触发生。 这项研究计划的一个关键要素是高度的 在技术和概念层面上的互动和协作， 在组成研究团队的科学家中。