Loss of motor cortical inputs to the red nucleus after central nervous system disorders in non-human primates

The premotor (PM) and primary motor (M1) cortical areas broadcast voluntary motor commands through multiple neuronal pathways, including the corticorubral projection that reaches the red nucleus (RN). However, the respective contribution of M1 and PM to corticorubral projections as well as its plasticity following motor disorders or injuries are not known in non-human primates. Here, we quantified the density and topography of axonal endings of the corticorubral pathway in RN in intact monkeys, as well as in monkeys subjected to either cervical spinal cord injury (SCI), Parkinson’s disease (PD)-like symptoms or primary motor cortex injury (MCI). Twenty adult macaque monkeys were injected with the biotinylated dextran amine (BDA) anterograde tracer either in PM or in M1. We developed a semi-automated algorithm to reliably detect and count axonal boutons within the magnocellular (mRN) and parvocellular (pRN) subdivisions of RN. In intact monkeys, PM and M1 preferentially target the medial part of the ipsilateral pRN, reflecting its somatotopic organization. PM’s projection to the ipsilateral pRN is denser than M1’s, matching previous observations for the corticotectal, corticoreticular, and corticosubthalamic projections (Fregosi et al., 2018, 2019; Borgognon et al., 2020). In all three types of motor disorders, there was a uniform and strong decrease (near loss) of the corticorubral projections from PM and M1. The RN may contribute to functional recovery after SCI, PD and MCI, by reducing direct cortical influence. This reduction possibly privileges direct access to the final output motor system, via emphasis on the direct corticospinal projection.