FUNCTIONAL NEUROANATOMY OF A MOVEMENT DISORDER

运动障碍的功能神经解剖学

• 批准号: 3402450
• 负责人: LUCY L BROWN
• 金额: $ 20.11万
• 依托单位: ALBERT EINSTEIN COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-09-09 至 1988-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3402450
• 关键词: Parkinson's disease; autoradiography; basal ganglia; brain mapping; brain metabolism; caudate nucleus; disease /disorder model; dopamine; experimental brain lesion; glucose metabolism; histopathology; limb movement; neural information processing; neuroanatomy; putamen; radiotracer; sensory cortex; somesthetic sensory cortex; stimulus /response; touch

The general hypothesis is that an important function of the basal ganglia is the processing of sensory as well as motor information to select and facilitate movements in normal states. Because striatal function must depend upon afferent information, the proposed studies define some aspects of this afferent information. Abnormal processing of sensory information in striatum may contribute to the abnormalities seen in Parkinson's disease and several other movement disorders, e.g. Huntington's and dystonias. More specifically, particular aspects of sensory, and parameters of motor function may be affected in the basal ganglia by the loss of dopamine in Parkinson's disease. These studies use C14 deoxyglucose autoradiographic mapping techniques to identify a tactile stimulus as a significant functional event in basal ganglia, to map and quantify the stimulus response throughout the basal ganglia, thalamus and cortex, and to compare this response to muscle afferent stimulation, passive movement and a trained movement of a limb. The somatosensory stimulus intensity will be varied to characterize the normal basal ganglia input-output functions of large groups of neurons, movement amplitude will be varied to confirm that it is a significant parameter processed by basal ganglia. These functions will then be analyzed for their dependence on dopamine for normal processing (metabolic response) in the motor system. The rat model of Parkinson's disease will be used. Lesions of the substantia nigra will be made to selectively damage the dopamine cells with 6 OH dopamine. C14 deoxyglucose studies of the tactile stimulus, of the muscle afferent stimulus, and trained movement will be carried out in the lesion condition. In each of these conditions, not only will basal ganglia metabolism be analyzed in detail, but also metabolism in cortex, thalamus and multiple other brain regions and spinal cord will be analyzed. The contribution of somatosensory cortex to basal ganglia responses under the somatosensory stimulus conditions will also be studied by making an ibotenic acid lesion of the cortex. An overall goal of these studies is to provide data and an approach that can be applied to a variety of animal models of movement disorders, e.g. genetic dystonia (rat model) and the promate MPTP model of Parkinson's disease. This approach may ultimately be applicable to PET studies of human movement disorders.

一般假设是基底神经节的重要功能 是感官的处理以及要选择的电动机信息吗？ 促进正常状态的运动。 因为纹状体功能必须 取决于传入的信息，拟议的研究定义了某些方面 这些传入信息。 感觉信息的异常处理 在纹状体中，可能导致帕金森氏病的异常 以及其他几种运动障碍，例如亨廷顿和肌张力纳斯。 更具体地说，感官的特定方面和电动机的参数 在基底神经节中，功能可能会因多巴胺的损失而影响 帕金森氏病。 这些研究使用C14脱氧葡萄糖放射自显影 映射技术以识别触觉刺激为重要 基底神经节中的功能事件，以绘制和量化刺激 整个基底神经节，丘脑和皮层的反应，并比较 这种对肌肉传入刺激，被动运动和A的反应 肢体的训练运动。 体感刺激强度将是 变化以表征正常的基底神经节输入输出功能 大量神经元，运动振幅将有所不同，以确认 这是基底神经节处理的重要参数。 这些功能 然后，将分析其对正常多巴胺的依赖性 电机系统中的处理（代谢响应）。 大鼠模型 帕金森氏病将被使用。 黑质的病变将是 用6个OH多巴胺有选择地损害多巴胺细胞。 C14 肌肉传入的触觉刺激的脱氧葡萄糖研究 刺激和训练的运动将在病变中进行 健康）状况。 在每种情况下，不仅基底神经节 代谢可详细分析，但在皮质，丘脑中也代谢 将分析其他多个大脑区域和脊髓。 这 体感皮质对基底神经节反应的贡献 还将研究体感刺激条件 皮质的依靠烯酸病变。 这些研究的总体目标是 提供数据和可以应用于各种动物的方法 运动障碍模型，例如遗传肌张力障碍（大鼠模型）和 帕金森氏病的诺言MPTP模型。 这种方法可能最终是 适用于人类运动障碍的宠物研究。