Crossed reflex pathways and their role during locomotor behavior in mice

运动行为被称为中枢模式生成器(CPG)的脊髓神经元间回路和感觉反馈的综合作用所控制。行走的关键特征之一是左腿和右腿交替的步进运动，这是慢速/中速时最常见的运动行为。用遗传学和生理学方法对小鼠的研究已经确定了位于Rexed板层的几类特殊的脊髓中间神经元，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，连合中间神经元在脊髓一侧传递来自CPG的信息，以协调对侧的活动，从而为行走时严格的交替步态模式奠定基础。尽管有大量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信息，但来自一条腿的感觉信息通过什么途径影响对侧腿的运动(交叉反射)尚不清楚。特别是，交叉性反射通路中连合中间神经元的参与尚未在小鼠中得到描述。然而，以猫为模型动物，对交叉反射通路进行了详细的描述。猫的研究表明，交叉反射通路也涉及位于Rexed Lamina VIII的连合中间神经元，它们的轴突通过腹侧连合穿过脊髓中线，就像小鼠传递CPG信息的连合中间神经元一样。然而，将局部CPG活动的信息从一侧脊髓传递到对侧的连合中间神经元是否也参与了交叉反射通路，以及这些通路在运动行为中的作用，目前尚不清楚。这项研究计划的结果将为深入了解小鼠的交叉反射通路，并进一步解决它们在运动中的作用。它将使半个多世纪以来在猫的连合反射通路上获得的洞察力与在老鼠身上使用最新基因技术的更新发现相结合。这个项目的最终结果将极大地促进我们对左右后腿如何由神经系统协调以及不同的连合通路所起的具体作用的了解。

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.