Crossed reflex pathways and their role during locomotor behavior in mice

运动行为被认为是由脊髓神经元间回路（称为中央模式发生器（CPG））和感觉反馈的综合作用控制的。步行的一个关键特性是左腿和右腿的交替步进运动，步行是以缓慢/中等速度进行的最常见的运动行为。使用遗传和生理方法对小鼠进行的研究已经表征了位于Rexed椎板VIII中的几类专门的脊髓中间神经元，其轴突通过腹侧连合投射到脊髓的对侧（连合中间神经元）。这些研究表明，连合中间神经元从一侧的CPG传递信息，以协调对侧的活动，从而在行走过程中形成严格的交替步进模式。尽管关于连合中间神经元的细胞生理学及其在行走过程中的作用的大量信息，来自一条腿的感觉信息影响对侧腿的运动（交叉反射）的途径尚不清楚。特别是，连合中间神经元参与交叉反射通路尚未在小鼠中描述。然而，交叉反射通路已经使用猫作为模型动物进行了详细描述。在猫中已经显示，交叉反射通路也涉及位于Rexed椎板VIII中的连合中间神经元，并且它们的轴突通过腹侧连合穿过脊髓的中线，就像在小鼠中传递CPG信息的连合中间神经元一样。然而，是否连合中间神经元，从一侧的脊髓到对侧的局部CPG活动的信息也涉及交叉反射通路，以及这些通路在运动行为中的作用，是未知的。这项研究计划的结果将提供对小鼠交叉反射通路的深入了解，并进一步解决它们在运动过程中的作用。它将使超过半个世纪的见解获得的连合反射途径描述的猫与最近的发现，使用最新的遗传技术在小鼠中的综合。这个项目的最终结果将大大推进我们的知识，左，右后腿是如何协调的神经系统和不同的连合通路发挥的具体作用。

Locomotor behavior is known to be controlled by the integrated action of a spinal interneuronal circuit, referred to as the central pattern generator (CPG), and sensory feedback. One of the key properties of walking, the most common locomotor behavior at slow/moderate speed, is the alternating stepping movement of the left and right legs. Studies on mice using genetic and physiological approaches have characterized several classes of specialized spinal interneurons located in the Rexed Lamina VIII, whose axons project to the contralateral side of the spinal cord (commissural interneurons) through the ventral commissure. These studies suggest that the commissural interneurons transfer information from the CPG on one side of the spinal cord to coordinate the activity of the contralateral side, thereby underlying strict alternating stepping pattern during walking. Despite a large volume of information regarding the cellular physiology of commissural interneurons and their role during walking, pathways by which sensory information from one leg affects the movement of the contralateral leg (crossed reflexes) are not clear. In particular, the involvement of commissural interneurons in crossed reflex pathways is not yet described in mice. However, crossed reflex pathways have been described in detail using cat as the model animal. It has been shown in cats that crossed reflex pathways also involve commissural interneurons located in Rexed Lamina VIII, and that their axons cross the midline of the spinal cord through the ventral commissure, just as the commissural interneurons transmitting CPG information in mice. Nevertheless, whether the commissural interneurons that transfer information of local CPG activity from one side of the spinal cord to the contralateral side are also involved in crossed reflex pathways, and the role of these pathways during motor behavior, is not known. The results of this research program will provide insight into crossed reflex pathways in mice and further address their role during locomotion. It will enable the synthesis of more than half a century of insights gained on commissural reflex pathways described in cats with more recent findings using up to date genetic techniques in mice. The final outcome of this project will significantly advance our knowledge of how left and right hind legs are coordinated by the nervous system and what specific role different commissural pathways play.