Central Control of Movement

描述(由申请人提供)： 我们的长期目标是确定负责中枢产生和控制自主运动的神经底物。在这项提案中，我们将探索这种底物的一个主要组成部分-初级运动皮质(M1)。在最近的解剖学实验过程中，我们发现M1不是一个统一的区域，而是有两个细分。M1的“新”细分只存在于一些猴子、类人猿和人类身上。它包含带有轴突的输出神经元，这些轴突下降到脊髓，并与运动神经元直接连接。这些神经元被称为皮质运动神经元(CM)细胞。相比之下，M1的“旧”细分是大多数哺乳动物物种的标准。旧M1包含下至脊髓的输出神经元，但仅通过与脊髓中间神经元的相互作用间接影响运动神经元。M1包含两个细分的证明提出了一个重要的问题--在旧的和新的M1中表示和控制的运动方面是否不同？存在用于识别CM细胞的生理学方法。此外，我们有一个独特的行为范式，它使我们能够定义在手腕运动期间皮质神经元活动中编码的运动方面。我们的范例，连同CM细胞的生理学鉴定，将使我们能够回答一个关键的问题-CM细胞向运动神经元发送下行命令的性质是什么？为了解决这些问题，我们将按照我们的范式训练猴子，该范式将与运动生成相关的3个参照系分开-肌肉活动、关节运动(内在参数)和动作方向(外在参数)。然后，我们将记录任务期间M1中单个神经元的活动。我们将取样旧M1和新M1，它们位于中央前回表面的皮质中，埋在中央前沟的前岸。此外，我们还将记录10-12块长期植入前臂的肌肉的活动情况。我们将使用尖峰触发的肌肉活动平均值来识别CM细胞。这一分析的结果将使我们能够确定：i)M1神经元发出的运动命令的性质，对运动行为有直接影响；ii)旧的和新的M1中表示和控制的运动方面。总体而言，我们提出的实验结果将为M1的功能、其细分及其在运动计划、生成和控制中的作用提供新的信息。 公共卫生相关性： 拟议的实验对退伍军人管理局的患者护理任务具有直接的临床意义。我们计划研究初级运动皮质的功能组织。这一领域对自愿流动的正常规划、产生和控制至关重要。中风或创伤性脑损伤对这一区域的损害可能会导致运动障碍，甚至身体某一部分完全瘫痪。我们的结果可能会对未来通过新的康复程序或通过使用神经假体设备恢复运动功能的尝试产生重要影响。这种恢复功能的新方法受到阻碍，部分原因是对通常产生运动的运动指令的性质缺乏了解。拟议研究的结果将提供其中一些关键信息。

DESCRIPTION (provided by applicant): Our long-term goal is to define the neural substrate that is responsible for the central generation and control of voluntary movement. In this proposal we will explore one major component of this substrate- the primary motor cortex (M1). In the course of recent anatomical experiments, we discovered that M1 is not a uniform area, but rather has two subdivisions. The "New" subdivision of M1 is only present in some monkeys, great apes and humans. It contains output neurons with axons that descend to the spinal cord and make direct connections with motoneurons. These neurons are termed cortico-motoneuronal (CM) cells. In contrast, the "Old" subdivision of M1 is the standard for most mammalian species. Old M1 contains output neurons that descend to the spinal cord, but influence motoneurons only indirectly through interactions with spinal interneurons. The demonstration that M1 contains two subdivisions raises an important question- Do the aspects of movement represented and controlled in Old and New M1 differ? Physiological methods exist for identifying CM cells. In addition, we have a unique behavioral paradigm which enables us to define the aspect of movement encoded in the activity of cortical neurons during wrist movement. Our paradigm, along with the physiological identification of CM cells, will allow us to answer a critical question- What is the nature of the descending commands that CM cells send to motoneurons? To address these questions, we will train monkeys on our paradigm which dissociates 3 reference frames associated with movement generation- muscle activity, joint movement (intrinsic parameters) and direction of action (an extrinsic parameter). Then, we will record the activity of single neurons in M1 during the task. We will sample Old M1 and New M1 which lie in cortex on the surface of the precentral gyrus and buried in the anterior bank of the precentral sulcus. In addition, we will record the activity of 10-12 chronically implanted muscles in the forearm. We will use spike-triggered averaging of the muscle activity to identify CM cells. The results from this analysis will enable us to determine: i) the nature of the motor commands issued by M1 neurons with a direct influence on motor behavior and ii) the aspects of movement represented and controlled in Old and New M1. Overall, the results from our proposed experiments will provide novel information about the functions of M1, its subdivisions and its role in the planning, generation and control of movement. PUBLIC HEALTH RELEVANCE: The proposed experiments have direct clinical relevance for the VA patient care mission. We plan to study the functional organization of the primary motor cortex. This area is critical for the normal planning, generation and control of voluntary movement. Damage to this area through stroke or traumatic brain injury can result in movement impairments or even complete paralysis of a body part. Our results may have an important impact on future attempts to restore motor function either through new rehabilitation procedures or through the use of neural prosthetic devices. Such new approaches to the restoration of function are hampered, in part, by a lack of knowledge concerning the nature of the motor commands that normally generate movement. The results from the proposed studies will provide some of this critical information.