Crossed reflex pathways and their role during locomotor behavior in mice

众所周知，运动行为是由脊髓神经元间回路（称为中枢模式发生器（CPG））和感觉反馈的综合作用控制的。行走是慢速/中速下最常见的运动行为，其关键特性之一是左右腿的交替迈步运动。利用遗传学和生理学方法对小鼠进行的研究已经确定了位于Rexed VIII层的几类特殊的脊髓中间神经元，其轴突通过腹侧连接投射到脊髓的对侧（联合中间神经元）。这些研究表明，联合中间神经元将一侧脊髓CPG的信息传递给对侧脊髓，从而协调对侧脊髓的活动，从而导致行走过程中严格的交替行走模式。尽管有大量关于互交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，但一条腿的感觉信息影响对侧腿运动的途径（交叉反射）尚不清楚。特别是，交交中间神经元在交叉反射通路中的参与尚未在小鼠中描述。然而，交叉反射通路已经以猫为模型动物进行了详细的描述。研究表明，猫的交叉反射通路也涉及位于Rexed椎板VIII的交联中间神经元，它们的轴突穿过脊髓中线，通过腹侧交联，就像小鼠的交联中间神经元传递CPG信息一样。然而，将局部CPG活动信息从脊髓一侧传递到对侧的互交中间神经元是否也参与交叉反射通路，以及这些通路在运动行为中的作用尚不清楚。本研究项目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。它将使半个多世纪以来对猫的互交反射途径的见解与最近在老鼠身上使用最新遗传技术的发现结合起来。该项目的最终结果将大大提高我们对神经系统如何协调左后腿和右后腿以及不同连接途径发挥的具体作用的认识。

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.