Topographical and cell type-specific connectivity of rostral and caudal forelimb corticospinal neuron populations

Corticospinal neurons (CSNs) synapse directly on spinal neurons, a diverse assortment of cells with unique structural and functional properties necessary for body movements. CSNs modulating forelimb behavior fractionate into caudal forelimb area (CFA) and rostral forelimb area (RFA) motor cortical populations. Despite their prominence, the full diversity of spinal neurons targeted by CFA and RFA CSNs is uncharted. Here, we use anatomical and RNA sequencing methods to show that CSNs synapse onto a remarkably selective group of spinal cell types, favoring inhibitory populations that regulate motoneuron activity and gate sensory feedback. CFA and RFA CSNs target similar spinal neuron types, with notable exceptions that suggest that these populations differ in how they influence behavior. Finally, axon collaterals of CFA and RFA CSNs target similar brain regions yet receive highly divergent inputs. These results detail the rules of CSN connectivity throughout the brain and spinal cord for two regions critical for forelimb behavior. [Display omitted] •Forelimb corticospinal neurons (CSNs) preferentially innervate inhibitory spinal neurons•Caudal (CFA) and rostral (RFA) CSNs target distinguishable spinal populations•CFA and RFA CSNs send axon collaterals to many similar brain regions•CFA and RFA CSNs receive input from distinct brain regions Carmona et al. comprehensively characterize the connectivity of two distinct forelimb corticospinal populations within the brain and spinal cord. Both groups preferentially target inhibitory spinal neurons but are selective in the specific neuronal subtypes they innervate. These corticospinal populations form axon collaterals in similar brain regions but receive different inputs.