Cerebellar Deep Brain Stimulation

项目摘要/摘要 神经和神经精神疾病是世界范围内日益令人担忧的后果 通常是致命的，或者充其量也就是让患者丧失能力。不幸的是，大多数患有这些疾病的患者 疾病对目前的药物没有反应，在少数有效的病例中，它们也可以。 最终会产生抗药性。深部脑刺激(DBS)是一种神经外科方法，它已经 在传统药物无法选择的情况下，成为一种有效的治疗方法。然而，即使是星展银行也有 它的局限性，因为大量的人对治疗没有反应。使用人类进行的研究 动物模型表明，DBS目前被定向到的大脑位置并不是 总是足够的。作为寻找更好的大脑修复靶点的第一步，我们设计了一种 小鼠的遗传工具包，提供了一种通用的方法来生成严重运动的小鼠模型 疾病。该工具包基于控制大脑区域中神经回路的功能，该区域被称为 小脑，一种参与运动和认知功能的结构，也是发育中的一个敏感部位 脑部疾病清单。在Aim1中，我们将使用这些遗传模型的组合，高分辨率 在行为小鼠身上进行的解剖学和活体电生理学，以确定神经特征 不同的运动性疾病。在AIM2中，我们将使用这些神经签名作为生物标记物来测试 应用FAST提供靶向闭合环小脑DBS消除运动障碍的可行性 时刻到时刻的精确度。这项工作的最终目标是扭转 通过纠正大脑功能和恢复活动能力来治疗疾病。提供额外治疗的可能性 无法治愈的神经和神经精神疾病的选择将提供替代医疗保健 关于减少疾病影响和提高患者生活质量的考虑。

PROJECT SUMMARY/ABSTRACT Neurological and neuropsychiatric diseases are a growing concern worldwide as the consequences are often lethal, or at best they leave patients incapacitated. Unfortunately, most patients with these diseases do not respond to the current medications, and in the few cases that do work, they too can eventually develop drug resistance. Deep brain stimulation (DBS), a neurosurgical approach, has become an effective treatment when traditional medicines are not an option. However, even DBS has its limitations, as a large number of people do not respond to the treatment. Research using humans and animal models suggests that the current brain locations into which DBS is directed are not always adequate. As a first step towards identifying better targets for brain repair, we designed a genetic toolkit in mice that provides a versatile method for generating mouse models for severe motor disease. The toolkit is based on controlling the function of neural circuits in a brain region called the cerebellum, a structure involved in motor and cognitive function and a susceptibility site in a growing list of brain diseases. In Aim1, we will use a combination of these genetic models, high-resolution anatomy and in vivo electrophysiology conducted in behaving mice to define neural signatures for different motor diseases. In Aim2, we will use these neural signatures as biomarkers to test the feasibility of providing targeted close-loop cerebellar DBS to eliminate motor deficits with fast moment-to-moment precision. The ultimate goal of this work is to reverse the behavioral outcomes of disease by correcting brain function and restoring mobility. The availability of additional treatment options for incurable neurological and neuropsychiatric diseases will provide alternate healthcare considerations for reducing the impact of disease and improving the quality of life of affected patients.