Spinal motoneurons as active players in motor control

运动神经元是脊髓中的细胞，向肌肉发送神经冲动以刺激肌肉收缩，是唯一与中枢神经系统以外的非神经细胞直接接触的神经元。虽然行动的决定是由大脑发起的，但运动神经元是控制最基本的行为：运动的连接链中的最后一个神经元。运动神经元被组织成单独的柱子，支配特定的肌肉，从控制脚趾的肌肉到控制眼球运动的肌肉。运动神经元的激活会引发肌肉收缩，而影响运动神经元的许多疾病会导致进行性瘫痪和致命的瘫痪。过去的大多数研究都致力于了解运动神经元在健康和疾病中的细胞特性，因为它们一直被认为只是将运动指令转化为行动所必需的输出元素。然而，我最近的研究表明，运动神经元本身形成了一个相互连接的网络，其中输出元素相互连接，并形成一个兴奋环路，具有力输出放大的潜在作用。这项拟议的研究的目的是揭开运动神经元之间连接模式的细节。特别是，由于运动神经元的大小不同，小的运动神经元大多用于低强度的运动任务，如行走，而大的运动神经元在需要更大的力量或速度的情况下被调用，如在跳跃或举起重物时，我们将确定不同类型的运动神经元之间的连接的架构，既包括那些支配相同肌肉的运动神经元，也包括那些支配协同或拮抗肌肉的运动神经元。此外，我们知道运动神经元之间通过谷氨酸递质相互通信，我们将能够选择性地删除运动神经元中的谷氨酸，以损害兴奋性环路。然后，我们将进行生理和行为实验，以确定运动神经元兴奋环如何影响动物在各种运动任务中的表现，以及它的缺失是否会改变力输出。我们的发现，运动神经元可以被认为是运动生成的积极参与者，这一发现可能对许多影响运动系统的疾病的研究和管理有几个启示。事实上，与运动神经元变性相关的一些首发症状可能是由于运动神经元之间失去连接所致。这一发现可能最终导致有针对性的策略，以改善那些受运动性疾病影响的人的运动控制。

Motoneurons are cells in the spinal cord that send nerve impulses to muscles to stimulate their contraction and are the only neurons that make direct contact with non neuronal cells outside the central nervous system. While the decision of action is initiated in the brain, motoneurons are the last neurons in the chain of connections controlling the most essential of behaviours: movement.Motoneurons are organized into separate columns innervating specific muscles, from those controlling the toes, to those controlling eyeball movements. Motoneurons' activation triggers muscle contractions and the many diseases affecting motoneurons cause progressive and fatal paralysis. Most research efforts in the past have been devoted to understanding the motoneurons cellular properties, in health and disease, since they have always been considered a mere output element necessary for translating motor command into action. My recent research however shows that motoneurons themselves form an interconnected network in which the output elements are connected with each other and form an excitatory loop, that has the potential role of an amplifier of the force output. The aim of the proposed research is to unravel the details of the pattern of connectivity between motoneurons. In particular, since motoneurons come in different sizes, with small motoneurons mostly employed for low intensity motor tasks, like walking, and large motoneurons called into action where greater force or speed are needed, as in jumping or lifting heavy weights, we will determine the architecture of the connections between different type of motoneurons, both between those innervating the same muscles and those innervating synergist or antagonist muscles. Furthermore, we know that motoneurons communicate with each other via the transmitter glutamate and we will be able to delete it selectively in motoneurons, in order to impair the excitatory loop. We will then perform physiological and behavioural experiments in order to determine how the motoneuron excitatory loop affect the performance of the animals in a variety of motor tasks and whether its deletion can alter the force output. Our finding that motoneurons can be considered active players in the generation of movement may have several implications in the study and management of many diseases affecting the motor system. It is in fact possible that some of the first symptoms associated with motoneuron degeneration might be due to loss of connectivity between motoneurons. This finding might eventually lead to targeted strategies for improving motor control in those affected by motor diseases.