REAL TIME CELLULAR IMAGING OF SEIZURES

癫痫发作的实时细胞成像

• 批准号: 6698559
• 负责人: Steven Mark Rothman
• 金额: $ 17.92万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-04-01 至 2005-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6698559
• 关键词: brain electrical activity; brain imaging /visualization /scanning; brain morphology; confocal scanning microscopy; dendrites; electroencephalography; epilepsy; genetically modified animals; green fluorescent proteins; hippocampus; laboratory mouse; long term potentiation; memory; neocortex; neural plasticity; neurons

DESCRIPTION (provided by applicant): Over the past two decades basic and clinical neuroscientists have become interested in the anatomic and physiological changes in the central nervous system induced by neuronal activity. These changes, categorized as "neural plasticity" are believed to explain many normal phenomena, such as learning and memory. However, changes in brain structure and function may also be induced by pathological neuronal activity. There is an emerging literature suggesting that the excessive neuronal discharges associated with epilepsy can alter the structure of neurons without leading to neuronal death, but no one has determined the extent or the reversibility of these changes in single, identified central neurons. There are now optical techniques and transgenic mice expressing the green fluorescent protein (GFP) and variants that allow "online" tracking of the morphological changes in single neurons during and after in vivo and in vitro seizures. The experiments proposed in this application will begin to test the hypothesis that prolonged seizure discharges can alter the morphology of spines and dendrites in single neurons imaged in real time and that these changes may play a role in the termination of some types of seizures. These are important issues to resolve, because there is an ongoing controversy about the structural and functional consequences of different types of seizure disorders. More conventional histological analysis, which readily identifies neuronal death, lacks the power to resolve questions about subtle anatomic alterations at the level of single neurons and processes. This work is still in an exploratory stage, because the exact parameters required for long term imaging of in vivo and in vitro seizures have not been determined. When the exploaratory work described in this application has been carried out, it should be feasible to begin isolating the individual variables that account for seizure-induced neuronal alterations. This information will be essential in informing debate about more aggressive therapy for specific types of epilepsy.

描述（由申请人提供）： 在过去的二十年中，基本和临床神经科学家对神经元活性引起的中枢神经系统的解剖和生理变化感兴趣。这些变化被归类为“神经可塑性”可以解释许多正常现象，例如学习和记忆。但是，病理神经元活性也可能引起大脑结构和功能的变化。有新兴的文献表明，与癫痫相关的过度神经元排出可以改变神经元的结构而不会导致神经元死亡，但没有人确定这些变化在单个，鉴定出的中心神经元中这些变化的程度或可逆性。现在有光学技术和转基因小鼠表达绿色荧光蛋白（GFP）和变体，可以在体内和体外癫痫发作期间和之后“在线”跟踪单神经元的形态变化。本应用程序中提出的实验将开始检验以下假设：延长的癫痫发作可以改变实时成像的单个神经元中刺和树突的形态，并且这些变化可能在终止某些类型的癫痫发作中起作用。这些是要解决的重要问题，因为关于不同类型的癫痫发作的结构和功能后果存在持续的争议。更常规的组织学分析很容易识别神经元死亡，它缺乏解决有关单个神经元和过程水平上微妙解剖变​​化的问题的能力。这项工作仍处于探索阶段，因为尚未确定体内和体外癫痫发作所需的确切参数。当已经进行了本应用中描述的剥削工作时，开始隔离癫痫发作诱导的神经元改变的个别变量应该是可行的。该信息对于告知有关特定类型癫痫的更具积极疗法的辩论至关重要。