Abstract
The corticospinal (CS) tract emerged and evolved in mammals, and is essentially involved in voluntary movement. Over its phylogenesis, CS innervation gradually invaded to the ventral spinal cord, eventually making direct connections with spinal motoneurons (MNs) in higher primates. Despite its importance, our knowledge of the origin of the direct CS-MN connections is limited; in fact, there is controversy as to whether these connections occur in subprimate mammals, such as rodents. Here we studied the retrograde transsynaptic connection between cortical neurons and MNs in mice by labeling the cells with recombinant rabies virus. On postnatal day 14 (P14), we found that CS neurons make direct connections with cervical MNs innervating the forearm muscles. Direct connections were also detected electrophysiologically in whole cell recordings from identified MNs retrogradely-labeled from their target muscles and optogenetic CS stimulation. In contrast, few, if any, lumbar MNs innervating hindlimbs showed direct connections on P18. Moreover, the direct CS-MN connections observed on P14 were later eliminated. The transient CS-MN cells were distributed predominantly in the M1 and S1 areas. These findings provide insight into the ontogeny and phylogeny of the CS projection and appear to settle the controversy about direct CS-MN connections in subprimate mammals.