Rhesus macaque versus rat divergence in the corticospinal projectome

We used viral intersectional tools to map the entire projectome of corticospinal neurons associated with fine distal forelimb control in Fischer 344 rats and rhesus macaques. In rats, we found an extraordinarily diverse set of collateral projections from corticospinal neurons to 23 different brain and spinal regions. Remarkably, the vast weighting of this “motor” projection was to sensory systems in both the brain and spinal cord, confirmed by optogenetic and transsynaptic viral intersectional tools. In contrast, rhesus macaques exhibited far heavier and narrower weighting of corticospinal outputs toward spinal and brainstem motor systems. Thus, corticospinal systems in macaques primarily constitute a final output system for fine motor control, whereas this projection in rats exerts a multi-modal integrative role that accesses far broader CNS regions. Unique structural-functional correlations can be achieved by mapping and quantifying a single neuronal system’s total axonal output and its relative weighting across CNS targets. •The entire projectome of the corticospinal motor system is mapped in rats and monkeys•The rat system elaborately collateralizes and integrates sensorimotor systems•The primate system is far more restricted in accessing direct motor execution•These differences between species have important implications for translational research Sinopoulou et al. map the entire projection network of the corticospinal motor system in rats and monkeys, including all collaterals. They find extensive corticospinal collateralization in rats yet far more direct corticospinal convergence on the spinal cord in monkeys. These findings have important implications for translational research.