Motor Cortex Projections To Red Nucleus And Pons Have Distinct Functional Roles In The Mouse

Pyramidal tract neurons (PTNs) are fundamental elements for motor control. However, it is largely unknown if PTNs are segregated into different subtypes with distinct roles in movement performance. Using anatomical, electrophysiological and optogenetics tools, we analyzed in both sexes mice motor cortex, PTNs projecting to red and pontine midbrain nuclei, which are important hubs connecting cerebral cortex and cerebellum playing a critical role in the regulation of movement. We reveal that vast majority of M1 neurons projecting to the red and pontine nuclei constitutes different populations. Corticopontine neurons have higher conduction velocities and morphologically, a most homogeneous dendritic and spine distributions along cortical layers. Optogenetically inhibiting either kind projection, differentially affects forelimb movement onset and execution in a lever press task, but only the activity of corticopontine neurons is significantly correlated with trial-by-trial variations in reaction time. The results indicate that cortical neurons projecting to the red and pontine nuclei constitute distinct functional and anatomical pathways and they contribute differently to sensorimotor integration, suggesting that layer 5 output neurons are functionally compartmentalized generating, in parallel, different downstream coding.