What language does the motor cortex use to speak to motoneurons?

描述（由申请人提供）：运动皮层使用什么语言与运动神经元交谈？初级运动皮层（M1）是向脊髓发出下行命令以产生运动输出的主要来源。大约50%的额叶皮质脊髓神经元起源于M1。一组特殊的皮质脊髓神经元是皮质运动神经元（CM细胞），它们与运动神经元有直接联系。我们将使用行为学、电生理学和解剖学方法相结合来研究CM细胞。我们建议提供，第一次，一个明确的和一致的看法，从CM细胞的运动神经元的信号。我们将使用肌电图（EMG）活动的尖峰触发平均（SpTA）来识别CM细胞及其靶肌肉。CM细胞及其靶肌肉的活性将被研究与多方向手腕任务中涉及的手腕运动的关系，该多方向手腕任务能够分离手腕运动的内在（肌肉样）和外在（运动样）参数。先前的研究已经表明，内在和外在参数都存在于M1活性中（Kakei等人，1999年）。解释“肌肉”和“运动”同时存在的一种方法是等级制度的存在。层次假说将预测CM细胞活性是肌肉样的，而非CM细胞活性是运动样的。换句话说，对运动神经元的直接输入是一种不需要翻译的语言。另一种选择是，肌肉样和运动样活动的混合物到达运动神经元，并用于在不同条件下产生运动。这个项目将确定哪个假设是正确的。我们还将首次记录CM细胞投射到腕部肌肉运动神经元的位置和分布。我们将使用狂犬病病毒的跨神经元转运来确定CM细胞在运动皮层中的位置，该运动皮层影响腕关节拮抗肌;桡侧腕屈肌和桡侧腕伸肌。如果时间允许，我们将比较CM细胞在幼稚动物中的分布与那些经过训练以执行熟练手腕任务的动物中的分布。这个实验将使我们能够确定是否广泛的训练改变了M1中CM细胞的皮层区域。 公共卫生相关性：项目叙述我们建议，第一次，提供一个清晰和一致的观点，从初级运动皮层的脊髓运动神经元的信号。从拟议的实验结果将解决有关运动皮层的组织和功能，其在运动的产生和控制的作用和运动皮层输出的性质的基本问题。这些结果可以提供对M1损伤后运动功能丧失的深入了解，并导致新的康复方法。此外，这些结果对于提供神经假体装置的设计中所需的信息将是重要的，所述神经假体装置使用来自运动皮层的信号来控制机器人装置或控制肌肉活动的电刺激以恢复运动功能。

DESCRIPTION (provided by applicant): What language does the motor cortex use to speak to motoneurons? The primary motor cortex (M1) is a major source of descending commands to the spinal cord for generating motor output. Approximately 50% of the corticospinal neurons from the frontal lobe originate from M1. A special set of these corticospinal neurons are corticomotoneural (CM cells) which have direct connections to motoneurons. We will investigate CM cells using a combination of behavioral, electrophysiological and anatomical methods. We propose to provide, for the first time, a clear and consistent view of signaling from CM cells to motoneurons. We will identify CM cells and their target muscles using spike-triggered averaging (SpTA) of electromyographic (EMG) activity. The activity of CM cells and their target muscles will be investigated in relation to wrist movements involved in a multi-directional wrist task capable of dissociating intrinsic (muscle-like) and extrinsic (movement-like) parameters of wrist movement. Previous studies have shown that both intrinsic and extrinsic parameters are present in M1 activity (Kakei et al., 1999). One way to explain the presence of both "muscles" and "movements" is the existence of a hierarchy. The hierarchy hypothesis would predict that CM cell activity is muscle like and non-CM cell activity is movement like. In other words, direct input to motoneurons is in a language that does not need to be translated. The alternative is that a mixture of muscle-like and movement-like activity reaches the motoneuron and is used to create movements under different conditions. This project will determine which hypothesis is correct. We will also document, for the first time, the location and distribution of CM cells projecting to wrist muscle motoneurons. We will use the transneuronal transport of rabies virus to define the location of CM cells in the motor cortex that influence antagonist wrist muscles; flexor carpi radialis and extensor carpi radialis. If time permits, we will compare the distribution of CM cells in naive animals to those of animals trained to perform a skilled wrist task. This experiment will enable us to determine whether extensive training alters the cortical territory of CM cells in M1. PUBLIC HEALTH RELEVANCE: Project Narrative We propose to provide, for the first time, a clear and consistent view of signaling from primary motor cortex to spinal motoneurons. Results from the proposed experiments will address fundamental issues about the organization and function of motor cortex, its role in the generation and control of movements and the nature of motor cortex output. These results can provide insight into loss of motor functions following damage to M1 and lead to new rehabilitation approaches. Further, these results will be important for providing information necessary in the design of neuroprosthetic devices which use signals from the motor cortex to control robotic devices or control electrical stimulation of muscle activity to restore motor function.