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

描述（由申请人提供）：运动皮层用什么语言与运动神经元对话？初级运动皮层（M1）是向脊髓下行指令的主要来源，以产生运动输出。额叶约50%的皮质脊髓神经元来源于M1。一组特殊的皮质脊髓神经元是皮质神经细胞（CM细胞），它与运动神经元有直接的联系。我们将结合行为学、电生理学和解剖学的方法来研究CM细胞。我们首次提出了CM细胞向运动神经元传递信号的清晰一致的观点。我们将使用肌电图（EMG）活动的峰值触发平均（SpTA）来识别CM细胞和它们的目标肌肉。CM细胞及其靶肌肉的活动将被研究与手腕运动有关的多向手腕任务，该任务能够分离手腕运动的内在（肌肉样）和外在（运动样）参数。先前的研究表明，M1活性中既有内在参数，也有外在参数（Kakei et al., 1999）。解释“肌肉”和“动作”同时存在的一种方法是存在等级制度。层次假设预测CM细胞的活动是肌肉样的，而非CM细胞的活动是运动样的。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。另一种方法是，类似肌肉和类似运动的混合活动到达运动神经元，并用于在不同条件下产生运动。这个项目将决定哪个假设是正确的。我们也将首次记录CM细胞投射到手腕肌肉运动神经元的位置和分布。我们将使用狂犬病毒的跨神经元转运来确定CM细胞在运动皮质中影响拮抗剂腕肌的位置；桡侧腕屈肌和桡侧腕伸肌。如果时间允许，我们将比较CM细胞的分布在幼稚的动物和那些受过训练的动物执行一个熟练的手腕任务。该实验将使我们能够确定广泛的训练是否会改变M1中CM细胞的皮质区域。

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.