Mapping the corticoreticular pathway from cortex-wide anterograde axonal tracing in the mouse

Abstract

The corticoreticular pathway (CRP) has been implicated as an important mediator of motor recovery and rehabilitation after central nervous system damage. However, its origins, trajectory and laterality are not well understood. This study mapped the mouse CRP in comparison with the corticospinal tract (CST). We systematically searched the Allen Mouse Brain Connectivity Atlas ((C) 2011 Allen Institute for Brain Science) for experiments that used anterograde tracer injections into the right isocortex in mice. For each eligible experiment (N=607), CRP and CST projection strength were quantified by the tracer volume reaching the reticular formation motor nuclei (RFmotor) and pyramids respectively. Tracer density in each brain voxel was also correlated with RFmotor versus pyramids projection strength to explore the relative trajectories of the CRP and CST. We found significant CRP projections originating from the primary and secondary motor cortices, anterior cingulate, primary somatosensory cortex and medial prefrontal cortex. Compared with the CST, the CRP had stronger projections from each region except the primary somatosensory cortex. Ipsilateral projections were stronger than contralateral for both tracts (above the pyramidal decussation), but the CRP projected more bilaterally than the CST. The estimated CRP trajectory was anteromedial to the CST in the internal capsule and dorsal to the CST in the brainstem. Our findings reveal a widespread distribution of CRP origins and confirm strong bilateral CRP projections, theoretically increasing the potential for partial sparing after brain lesions and contralesional compensation after unilateral injury. SIGNIFICANCEThe corticoreticular pathway (CRP) provides volitional input to brainstem nuclei that generate walking command signals, facilitate balance and direct limb movements. Upregulation of this pathway appears to be a central mechanism of movement recovery after brain and spinal cord injury, but its anatomy is not well understood. We showed that the mouse CRP originates from widespread parts of the cortex, including non-motor regions, that it projects strongly to both sides of the brainstem, and that its projections are more distributed and bilateral than the corticospinal tract. These findings suggest that the CRP may be particularly resilient to complete disruption.