NEURAL CORRELATES OF EXERCISE THERAPY IN PD MODEL

PD 模型中运动治疗的神经相关性

• 批准号: 6785032
• 负责人: DONALD JAY WOODWARD
• 金额: $ 28.61万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-08-01 至 2008-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6785032
• 关键词: Parkinson's disease; apomorphine; behavior test; behavioral /social science research tag; corpus striatum; disease /disorder model; dopamine; electrodes; electrophysiology; exercise; functional ability; laboratory rat; limb movement; nervous system disorder therapy; neuromuscular system; neurons; neurophysiology; physical therapy; sensorimotor system; single cell analysis; substantia nigra

The goal of this project is to characterize the neurophysiological changes induced during the recovery of function in awake behaving rat by the depletion of dopamine in striatum by the unilateral administration of 6-hydroxydopamine as a model for Parkinson's disease. Preliminary studies have shown that depletion of dopamine results in an elevation of resting firing rates of neurons in the neostriatum. This effect is maximum of the depleted side but is nearly equally apparent on the intact side with no depletion of DA. Activation of rotation activates reciprocal changes in neighboring neurons on both sides with no net changes in means rates, thus indicating the presence of an effective synaptic input to both intact and DA depleted striatum. An interpretation is that absence of dopamine induces a motor dysfunction directly on the affected side. This in turn activates a widespread motor recovery adaptive mechanism that engages both sides of the cortical striatal nigral thalamic system. Forced use of the limb on the DA depleted side by application of a cast to restrict use of the unaffected limb, specifically in the first 7 days after 6-OHDA, has recently been found to offer neuroprotection against 6-OHDA, and thus raised the possibility that the widespread bilateral elevation of activity may play both a neuroprotective as well as a compensatory role. An aim of this project is to record activity of populations of neurons recorded simultaneously from 64 microwires implanted bilaterally in striatum, substantia nigra reticulata/compacta, and forelimb sensorimotor cortex. These advanced recording procedures developed in this laboratory will determine activity of populations over the two weeks after 6-OHDA administration. Casting to restrict limb use will be done on both the DA depleted and intact side to compare effects of restriction of movement and to determine the neural signals during movements during tests of motor impairment. Casting will be done prior to 6-OHDA to test whether elevation of activity appears during the early period of motor reorganization and may serve to activate neuroprotection. Recordings made from dopamine neurons will test the emerging concept of a role in motor learning and reorganization. A prediction is that the novel movement patterns during forced use will produce many signals in striatum and cortex correlated with movement that are not present in over-trained circuits.

本研究的目的是以6-羟基多巴胺为帕金森病模型，研究纹状体内多巴胺耗竭引起的清醒行为大鼠在功能恢复过程中的神经生理变化。初步研究表明，多巴胺的耗竭会导致新纹状体神经元静息放电率的提高。这种影响在枯竭侧最明显，但在DA未枯竭的完好侧几乎同样明显。激活旋转激活两侧相邻神经元的相互变化，平均速率没有净变化，因此表明存在对完整和DA耗竭的纹状体的有效突触输入。一个 解释是，缺乏多巴胺会直接导致患侧的运动功能障碍。这反过来激活了一种广泛的运动恢复适应机制，该机制参与了皮质纹状体黑质丘脑系统的两侧。最近发现，强迫使用DA耗竭侧的肢体，通过石膏限制健侧肢体的使用，特别是在6-OHDA后的前7天，可以提供对6-OHDA的神经保护，因此提出了这样一种可能性，即广泛的双侧活动增加可能既起到神经保护作用，又起到代偿作用。该项目的一个目的是记录同时记录的双侧植入微丝的神经元群体的活动。 纹状体、黑质网状核/致密层和前肢感觉运动皮质。该实验室开发的这些先进的记录程序将确定6-OHDA给药后两周内人群的活动。限制肢体使用的铸型将在DA耗竭和完好的一侧进行，以比较限制运动的影响，并在运动障碍测试期间确定运动期间的神经信号。铸型将在6-OHDA之前进行，以测试在运动重组的早期是否出现活动增加，并可能有助于激活神经保护。由多巴胺神经元制成的录音将测试在运动学习和重组中扮演角色的新兴概念。一种预测是，强迫使用时的新运动模式将在纹状体和皮质产生许多与运动相关的信号，这些信号在过度训练的回路中是不存在的。