Physiological and molecular analysis of motor-area function.

为了了解额叶皮质运动区域的功能组织，我们计划并实施了一个综合研究项目。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，以促进每个项目的研究工作的相互发展，并完成了联合工作。经过深入的思想交流和协作工作，取得了以下成果：皮质-基底神经节回路功能组织的一个新方面已经被发现。虽然已经确定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和功能意义都不清楚。在本研究中，我们首先用生理技术绘制初级运动皮层，然后应用2小时的皮层内微刺激（ICMS）。随后立即对大脑进行灌注、切片并进行免疫组织化学处理，以确定脑电图（c-fos和jun-B）。同时对细胞进行脑啡肽免疫染色。IEG阳性细胞大部分Enkephalin阳性，提示从初级运动皮质突出的皮质纹状体细胞多属于间接通路。我们随后发现，大多数刺激辅助运动区后的IEG阳性细胞并不是脑啡肽阳性，这表明SMA向纹状体的投射主要属于直接通路。这些发现为皮质-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。在另一个项目中，我们分析了NMDA谷氨酸受体亚基在灵长类动物皮层运动区的分布。为此，我们首先在生理识别后标记皮层区域。随后，采用原位杂交方法找到NMDA受体的亚基epsilon1、epsilon2和xi。亚基分布在前额叶皮层、前运动皮层、初级运动皮层和体感觉皮层的不同皮层层差异很大。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