Crossed reflex pathways and their role during locomotor behavior in mice

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.