Cerebellar Deep Brain Stimulation

项目总结/摘要 神经系统和神经精神疾病是一个日益关注的世界范围内的后果， 通常是致命的，或者最多让病人丧失能力。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，在少数情况下，他们也可以工作， 最终产生抗药性。脑深部电刺激（DBS）是一种神经外科手术方法， 在传统药物无法使用的情况下，成为一种有效的治疗方法。然而，即使是DBS， 它的局限性，因为很多人对治疗没有反应。使用人类的研究 动物模型表明，目前脑深部电刺激的脑部位并不 总是足够的。作为确定更好的大脑修复目标的第一步，我们设计了一个 小鼠遗传工具包，提供了一种通用的方法，用于产生严重运动的小鼠模型， 疾病该工具包是基于控制大脑中一个称为“大脑皮层”的区域的神经回路的功能。 小脑，一个参与运动和认知功能的结构，也是生长中的易感部位。 脑疾病列表在Aim 1中，我们将使用这些遗传模型的组合，高分辨率 解剖学和体内电生理学在行为小鼠中进行，以定义用于 不同的运动疾病在Aim 2中，我们将使用这些神经特征作为生物标志物来测试 提供靶向闭环小脑DBS以快速消除运动缺陷的可行性 精确到每一刻这项工作的最终目标是扭转的行为结果， 通过纠正大脑功能和恢复活动能力来治疗疾病。额外治疗的可用性 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 减少疾病的影响和改善受影响患者的生活质量的考虑。

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.