Mossy cell network dysfunction in temporal lobe epilepsy

颞叶癫痫的苔藓细胞网络功能障碍

• 批准号: 8760220
• 负责人: Anh Bui
• 金额: $ 3.68万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-30 至 2016-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8760220
• 关键词: Age; Animal Model; Animals; Behavioral; Cells; Chronic; Cognitive deficits; Data; Detection; Development; Disease; Economic Burden; Electroencephalography; Epilepsy; Exhibits; Fiber; Goals; Hippocampus (Brain); Human; Impaired cognition; Implant; Injection of therapeutic agent; Ion Channel; Learning; Light; Link; Location; Memory; Memory impairment; Methods; Modeling; Monitor; Mus; Neurons; Opsin; Patients; Pattern; Phase; Physiologic pulse; Play; Population; Quality of life; Recurrence; Role; Seizures; Signal Transduction; System; Technology; Temporal Lobe Epilepsy; Testing; Time; Training; Work; cognitive function; cost; dentate gyrus; granule cell; in vivo; kainate; nervous system disorder; network dysfunction; novel; object recognition; optogenetics; public health relevance; selective expression; software development

DESCRIPTION (provided by applicant): With 5-10 cases of epilepsy per 1000 people in the world, and temporal lobe epilepsy making up over 66% of these cases, temporal lobe epilepsy is considered one of the most prevalent and serious neurological disorders. The annual economic burden of over $12.5 billion in the US alone adds to the considerable cost in the quality of life of epileptic patients, and calls for efforts to better understand the mechanisms underlying spontaneous seizures. A neuronal cell population that may play a key role in seizure activity is hippocampal mossy cells, which are critically important in the dentate gyrus excitatory network. This project proposes to test the hypothesis that mossy cells are central to amplifying and propagating hyperexcitable activity, and contribute to the development of debilitating epilepsy-related cognitive deficits. The hypothesis will be tested during the chronic epilepsy period of the intrahippocampal kainate epilepsy model. Alterations occurring in the dentate gyrus of the mouse hippocampus will be investigated using a combination of in vivo electrophysiological and closed-loop optogenetic methods, as well as learning and memory studies. Discerning the role of mossy cells in temporal lobe epilepsy and related cognitive impairments may open doors in the development of novel therapeutical approaches for this disorder.

描述（由申请人提供）： 世界上每1000人中有5-10例癫痫，颞叶癫痫占这些病例的66%以上，颞叶癫痫被认为是最普遍和严重的神经系统疾病之一。仅在美国，每年超过125亿美元的经济负担就增加了癫痫患者生活质量的可观成本，并要求努力更好地了解自发性癫痫发作的机制。在癫痫发作活动中可能起关键作用的神经元细胞群是海马苔藓细胞，其在齿状回兴奋性突触中至关重要。 网络该项目旨在验证苔藓细胞是放大和传播过度兴奋活动的核心，并有助于发展衰弱性癫痫相关认知缺陷的假设。将在海马内红藻氨酸盐癫痫模型的慢性癫痫期期间检验该假设。将使用体内电生理学和闭环光遗传学方法以及学习和记忆研究的组合来研究小鼠海马齿状回中发生的改变。识别苔藓细胞在颞叶癫痫和相关认知障碍中的作用，可能会为这种疾病的新治疗方法的发展打开大门。