Basal Ganglia Neurophysiology during DBS in Rats

大鼠 DBS 期间基底节神经生理学

• 批准号: 6647093
• 负责人: JING-YU CHANG
• 金额: $ 26.52万
• 依托单位: WAKE FOREST UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-01 至 2007-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6647093
• 关键词: Parkinson's disease; basal ganglia; behavior test; brain electrical activity; brain electronic stimulator; disease /disorder model; dopamine; experimental brain lesion; immunocytochemistry; laboratory rat; lenticular nucleus; neural information processing; neurons; neurophysiology; prosencephalon; psychomotor function; substantia nigra

DESCRIPTION (provided by applicant): Parkinson's disease (PD) is a degenerative neurological disorder affecting millions of patients all around the world. Renewed use of the deep brain stimulation (DBS) method provides a new opportunity for treating PD. A key issue to improve the treatment is to fully understand the neural mechanisms underlying the therapeutic effects of DBS. In this proposed study, two unique techniques developed in our laboratory: the chronic multiple-channel single unit recording and rat model of DBS, will be employed to study the neural responses in multiple basal ganglia regions during behaviorally effective DBS in rat model of Parkinsonism. A first objective is to establish a rodent model of DBS in Parkinsonian conditions. The effects of DBS will be evaluated in dopamine lesioned rats performing treadmill locomotion and limb use asymmetry tests. Locomotor d deficits during treadmill walking and imbalance usage of forelimb in vertical exploratory behaviors will develop after unilateral dopamine lesion. High frequency stimulation (HFS) of the subthalamic nucleus (STN) and the substantia nigra pars reticulata (SNr) will then be applied to alleviate these motor abnormalities. The degree of dopamine depletion in the basal ganglia will be detected by immunohistochemical staining of dopamine marker and this result will be correlated with the severity of motor deficits and DBS effects. Second, the basal ganglia neural responses following a dopamine lesion and during behaviorally effective HFS will be examined. Single neural activity and local field potential in the striatum globus pallidus, STN and SNr will be recorded simultaneously in a 64 channel recording system in the rat performing these behavioral tests. Neural responses following dopamine lesion will help us to understand the pathophysiologic process of developing Parkinsonian syndromes while the neural responses during behaviorally effective HFS will shed light on how DBS can restore normal information processing in the basal ganglia neural circuits that are disrupted following dopamine lesion. Several important improvements on recording and stimulation techniques will be made in cooperation with Biographic Inc. to achieve optimal conditions for high frequency stimulation and artifact free recording. The goal of this study is to explore the basic neural mechanism underlying the therapeutic effects of DBS and the knowledge obtained form this study will help us to improve the clinical treatment of PD with DBS method.

描述（由申请人提供）： 帕金森氏病（PD）是一种退化性神经疾病，影响了世界各地数百万患者。对深脑刺激（DBS）方法的更新使用为治疗PD提供了新的机会。改善治疗方法的一个关键问题是充分了解DBS治疗作用的神经机制。在这项拟议的研究中，我们的实验室中开发了两种独特的技术：将采用慢性多通道单位单位记录和DBS的大鼠模型，用于研究帕金森主义大鼠模型中行为有效的DBS期间多个基底神经节区域的神经反应。第一个目标是在帕金森氏症情况下建立DBS的啮齿动物模型。 DBS的作用将在多巴胺病变的大鼠进行跑步机运动和肢体使用不对称测试的情况下进行评估。在单侧多巴胺病变后，将在垂直探索行为中跑步机行走和前肢不平衡的使用过程中的运动缺陷。然后，将应用丘脑下核（STN）的高频刺激（HFS）和Nigra pars网状（SNR），以减轻这些运动异常。多巴胺标记物的免疫组织化学染色将检测到基底神经节中多巴胺的耗竭程度，该结果将与运动缺陷和DBS效应的严重程度相关。其次，将检查多巴胺病变后以及行为有效的HFS后的基底神经神经反应。纹状体pallidus，STN和SNR中的单个神经活动和局部场电位将同时记录在大鼠进行这些行为测试的64个通道记录系统中。多巴胺病变后的神经反应将有助于我们了解发展帕金森氏综合症的病理生理过程，而行为有效的HFS期间的神经反应将阐明DBS如何恢复基础神经节神经循环中的正常信息处理，这些神经神经回路在多巴胺病后受到干扰。将与传记公司合作进行记录和刺激技术的一些重要改进，以实现高频刺激和无伪影记录的最佳条件。这项研究的目的是探索DBS治疗作用的基本神经机制以及获得的知识形式，这项研究将有助于我们使用DBS方法改善PD的临床治疗。