Physiological and molecular analysis of motor-area function.

为了了解额叶皮质运动区的功能组织，我们计划并实施了一项综合性研究项目。我们以灵长类动物为实验动物，采用生理和分子相结合的方法进行了一系列实验。东北大学的研究人员访问了波士顿的麻省理工学院，麻省理工学院的教授访问了东北大学，推动了每个项目的研究工作的共同发展，并进行了联合工作。经过密集的思想交流和协作工作，取得了以下成果。皮质-基底节环的功能组织的一个新的方面已经被发现。尽管已证实基底神经节的输出分为直接通路和间接通路两部分，但它们与皮质运动区的关系及其功能意义尚不清楚。在本研究中，我们首先用生理学技术定位初级运动皮质，然后应用…更多的皮质内微刺激(ICMS)，持续2小时。随后立即进行脑灌流、切片和免疫组织化学处理，以确定IEG(c-fos和jun-B)。同时对细胞进行脑啡肽免疫组织化学染色。IEG阳性细胞脑啡肽大量阳性，提示初级运动皮质投射的皮质纹状体细胞大多属于间接通路。随后我们发现，在刺激辅助运动区后，大多数IEG阳性细胞不呈脑啡肽阳性，表明SMA向纹状体的投射主要属于直接通路。这些发现为了解皮质-基底神经节通路在运动控制中的功能作用提供了新的见解。在另一个单独的项目中，我们分析了NMDA谷氨酸受体亚单位在灵长类动物皮质运动区的分布。为此，我们首先在生理识别后标记大脑皮层区域。随后，采用原位杂交的方法找到了NMDA受体的亚基epsilon1、epsilon2和xi，其在前额叶、运动前、初级运动和躯体感觉皮质的不同皮质层中的分布有很大差异。较少

To understand functional organization of the motor areas in the frontal cortex, we planned and performed an integrative research project. Using primates as experimental animals, we conducted a series of experiments with a combined physiological and molecular approach.Researchers in Tohoku University visited MIT in Boston, and professors at MIT visited Tohoku University to advance mutual development of research works in each project, and joint works have done. As a result of intensive exchanges of ideas and collaborative works, the following results have been obtained. A novel aspect of functional organization of cortico-basal ganglia loops has been found. Although it has been established that the output from the basal ganglia is divided into two parts, direct and indirect pathway, neither their relationships with cortical motor areas nor their functional significance were known. ln the present study, we first mapped the primary motor cortex with physiological techniques, and then appli … More ed intracortical microstimulation (ICMS) for a period of 2 hrs. Immediately thereafter, brains were perfused, sectioned, and processed for immunohistochemistry to identify IEGs (c-fos and jun-B). At the same time, cells were immuno-stained for Enkephalin. IEG positive cells were found to be largely positive for Enkephalin, indicating that the cortico-striatal cells projecting from the primary motor cortex mostly belong to the indirect pathway. We subsequently found that a majority of IEG positive cells following stimulation of the supplementary motor area are not Enkephalin positive, indicating that the SMA projection to the striatum mainly belong to the direct pathway. These findings provide a new insight about functional roles of the cortico-basal ganglia pathway in motor control. In a separate project, we analyzed the distbution of subunits of NMDA glutamate receptors in cortical motor areas of primates. For this purpose, we first marked cortical areas after physiological identification. Subsequently, in situ hybridization method was applied to find subunits epsilon1, epsilon2, and xi of NMDA receptors.The subunit distribution differed greatly in different cortical layrs in the prefrontal, premotor, primary motor, and somatosensory cortex. Less