ANATOMY AND MOTOR FUNCTIONS OF THE MIDBRAIN

中脑的解剖结构和运动功能

• 批准号: 6243769
• 负责人: MICHAEL D CRUTCHER
• 金额: $ 16.51万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-05-01 至 1998-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6243769
• 关键词: Macaca nemestrina; Parkinson's disease; basal ganglia; brain mapping; central nervous system; central neural pathway /tract; disease /disorder model; dopamine receptor; glutamate receptor; immunocytochemistry; mesencephalon; methylphenyltetrahydropyridine; muscarinic receptor; neuropharmacology; pons; psychomotor function; synapses; tegmentum; thalamocortical tract

Pathways linking the midbrain tegmentum and basal ganglia have been long implicated in the control of movement. While it is suspected that pathologic involvement of these pathways accounts for some of the clinical signs of movement disorders, many of the basic features of their anatomical and physiologic relations to the basal ganglia have yet to be elucidated. This study will employ a correlated anatomical, neurochemical and physiological approach to determine the role of these connection in normal and pathologic movement in the primate. Our preliminary investigations in the rodent have localized a unique neuronal population in the midbrain tegmentum that is strongly interconnected with the basal ganglia (i.e., the midbrain extrapyramidal area, MEA). The topography and neurochemical identity of this cell group is distinct from that of surrounding neuronal subserves primarily motor functions. The first goal of this study is to provide a detailed characterization of midbrain efferents to the basal ganglia in the primate. We will determine the origin, neurochemical identity and synaptic termination of these connections. Immunohistochemical characterization of specific muscarinic, dopamine and glutamate receptor subtypes will serve to further differentiate these pathways from adjacent cell groups. The findings will provide a convectional and chemoarchitectonic map of the midbrain to guide the functional characterization of motor-related midbrain cell groups. The second goal of this study is to the define the motor functions of the MEA. Selective pharmacological activation or inactivation of this cell group will be performed in awake behaving monkeys so that its influence(s) on basal ganglia physiology and motor performance can be determined. In Parkinson's disease (PD) there is increased inhibitory output from the basal ganglia to the midbrain. We hypothesize that excessive inhibition of the MEA might be responsible for some of the motor symptoms of PD. The third goal of this study is to determine whether reversing this inhibition in monkeys made parkinsonian with MPTP will normalize the motor output of the basal ganglia and ameliorate the symptoms of PD. The results of these proposed studies will elucidate the neural and physiological substrates underlying the midbrain's mediation of motor behavior. They will also provide a better understanding of the pathophysiological basis for the presumed role of the midbrain in the motor dyscontrol of PD and in so doing identify a new potential target for the treatment of hypokinetic movement disorders.

连接中脑teggementum和基底神经节的途径已经很长 与移动的控制有关。 虽然怀疑 这些途径的病理参与造成了一些 运动障碍的临床迹象，其许多基本特征 与基底神经节的解剖学和生理关系尚未 阐明。 这项研究将采用相关的解剖学， 神经化学和生理方法来确定这些作用 灵长类动物的正常和病理运动的联系。 我们在啮齿动物中的初步调查已经定位了一个独特的 中脑teggenmum的神经元种群强烈 与基底神经节相互连接（即中脑锥形 区域，MEA）。 该细胞组的地形和神经化学身份 与周围的神经元亚基不同，主要是运动 功能。 这项研究的第一个目标是提供详细的 在中间脑对基底神经节的表征 灵长类动物。 我们将确定起源，神经化学身份和 这些连接的突触终止。 免疫组织化学 特定毒蕈碱，多巴胺和谷氨酸受体的表征 亚型将进一步区分这些途径与相邻 细胞组。 调查结果将提供对流和 中脑的化学结构图指导功能 与运动相关的中脑细胞组的表征。 第二个目标 这项研究是为了定义MEA的运动功能。 选择性 该细胞组的药理激活或灭活将是 在醒着的行为猴子中表演，以使其对基础的影响 可以确定神经节生理学和运动性能。 在帕金森氏病（PD）中，抑制性产量增加 基底神经节到中脑。 我们假设过度抑制 MEA的某些运动症状可能是PD的某些运动症状。 这项研究的第三个目标是确定是否扭转这一点 猴子的抑制作用使帕金森尼与MPTP的抑制作用将使 基底神经节的电动输出和改善PD的症状。 这些提出的研究的结果将阐明神经和 中脑介导的生理底物 行为。 他们还将更好地理解 中脑在中脑中的作用的病理生理基础 PD的电动机心电图，因此请确定一个新的潜在目标 用于治疗低迷运动障碍。