UC San Diego

This thesis addresses a basic question about the neural control of movement: how do interneurons in the ventral spinal cord govern motor output? To implement an action, the nervous system ultimately must send its commands through the motor neurons, which reside in the spinal cord. If motor neurons constitute the last site of processing, then spinal interneurons are a critical second-to-last regulator since they sit as inputs only one layer further upstream. However, though these cells have been extensively characterized at the level of genetics and development, they remain much less well understood in terms of function. This is largely for technical reasons: the spinal cord moves in concert with the body and it is therefore difficult to monitor the activity of its neurons while an animal is moving. The thesis attempts to improve our understanding by surmounting that technical obstacle. Chapter 1 details a multi-year effort to achieve recordings of extracellular signals from the lumbar spinal cord of freely-moving mice. I helped to develop a flexible electrode that, by accommodating the motions of the spinal tissue, allows for isolation of spikes from single units during motor behavior. Chapter 2 leverages and elaborates on this technique to try to resolve differences in spinal neuron firing patterns depending on behavioral context and cell identity. The chapter presents a hindlimb motor assay that I designed to monitor spinal neuron activity during a discrete, rather than rhythmic, behavior. It also presents preliminary evidence that a distinct class of spinal cord interneurons – the V1 inhibitory group – can be modulated with optogenetics during recordings. These insights are combined to look at population-level patterns by grouping neurons based on their electrophysiological signatures and correlations with movement. Finally, a short concluding chapter discusses future directions that intraspinal recording work might take and offers some reflections on the relationship of technical developments to discovery in neuroscience. In total, this thesis aims to shed light on spinal cord function by combining observations made at a new higher degree of specificity in three areas: with respect to signal (single unit), context (behavior), and identity (cell type).