Distinct limb and trunk premotor circuits establish laterality in the spinal cord

Motor behaviors, such as walking or running, rely on the precise temporal activation pattern of distinct muscles. The neuronal elements controlling these stereotyped motor routines are located in the spinal cord. Somatic motor neurons within the spinal cord send their axons in the periphery, innervating distinct muscle targets. Motor neurons controlling one particular muscle are clustered into motor neuron pools. In this study we revealed the spinal premotor circuits, which control the activity of motor neuron pools, which regulate muscles of the hind-limb and the back (axial muscles), using an intersectional approach between mouse genetics and viral tracing methods. We found that premotor networks controlling motor neurons innervating limb muscles, exhibit a completely different global structure than the ones regulating motor neurons innervating axial muscles, with the majority of premotor interneurons controlling limb-innervating motor neurons being located on the ipsilateral side of the spinal cord, with respect to the controlled muscle, where as in contrast, motor neurons innervating axial muscles are controlled by premotor circuits mainly located on the contralateral side of the spinal cord. More detailed analysis revealed that the limb- versus axial spinal premotor networks exhibit differences in distribution of inhibition and the progenitor-domain contribution to the different circuits. Furthermore, we describe two elements of the spinal motor system, which may explain the differences in premotor networks we found. One parameter is the location of the motor neuron pool within the spinal cord. Motor neurons innervating axial muscles are located in a domain, which is highly accessible by contralateral commissural interneurons, where as limb controlling motor neurons reside in a spinal domain, which receives less direct commissural input. Another feature, which may explain the differences on the premotor level, are the midline-crossing dendrites of the motor neurons innervating the axial muscles, allowing these motor neurons to receive monosynaptic input from contralateral, ipsilaterally-projecting interneurons, which would otherwise be off-limits. Limb innervating motor neurons do not exhibit midline-crossing dendrites, denying their direct synaptic access by these contralateral, ipsilaterally-projecting interneurons. In summary these two parameters correlate well with our observation of different laterality of axial- versus limb controlling premotor circuits.
Our study revealed that spinal premotor circuits, which control different aspects of motor behavior, are organized in a fundamentally distinct manner.