Movement is the outcome of signaling between the cortex, brainstem, spinal cord and peripheral nervous system onto the final modes of motor output – motor neurons and their target muscles. Simple motor tasks such as reaching for a cup of coffee involve complex neural calculations to selectively recruit and coordinate appropriate muscle and joint combinations. Spinal interneurons are believed to simplify this process by encoding specific patterns of muscle activation, known as ‘motor synergies.’ The deep dorsal horn of the spinal cord is an important area for generating motor synergies. Interneurons in this region receive descending cortical and peripheral sensory inputs and send outputs to motor neurons, suggesting that they integrate high-level cortical commands and sensory feedback for coordinated movements. Recent studies have demonstrated that spinal interneurons can elicit synergistic patterns of muscle activity in the absence of descending and peripheral inputs. This suggests that the spinal cord contains enough local computing power to generate compound movements. Investigations of these circuits have been insightful, however much remains to be learned of the mechanisms by which they direct motor output.

This dissertation describes a series of original work that aims to identify spinal premotor organization in relation their post-synaptic partners, as well as their transcriptional identities. The first chapter presents a new framework for the anatomical organization of functionally distinct spinal premotor networks. Contrary to previous knowledge, we found that these networks are spatially intermingled rather than segregated. In Chapter 2, we evaluate viral vectors for identifying dual-projecting neurons and conclude that Pseudorabies-Bartha is a suitable tool. In Chapter 3, we build circuit maps of synergistic and antagonistic premotor networks. We find that premotor neurons diverge to form dual projections onto multiple motor pools. Finally, in Chapter 4, we perform single-nuclei RNA sequencing of premotor neurons. We determine that they are predominantly ventral, an equal mix of excitatory and inhibitory, and express group-Z markers, which are indicative long-range projecting neurons.

In summary, this work enhances our knowledge of spinal premotor network organization, composition, and development, providing a new framework for the spatial arrangement of flexor and extensor premotor neurons.