The breadth of animal movements is mesmerizing. From the mountain goat’s nimble adaptive locomotion to the precision pounce of a cougar, and from the acrobatic parkour of squirrels to the delicate handling by racoons, how are such feats accomplished? The answers to this question are distributed throughout the nervous system and the body as a complex interaction of neural coding and biomechanics. But since the work of Sherrington and others over the last century, we know that the mammalian spinal cord can autonomously mediate simple behaviors such as walking, jumping, and limb withdrawal. We seek to define the roles of spinal neurons in selecting, executing, and linking together the elemental movements that can be built up into these behaviors. If spinal motor control is the final output of the mammalian nervous system, then understanding its mechanisms will provide fundamental insights into the neural logic of behavior.
We are guided by three key questions...
What are the cell types of the mammalian spinal cord? Using single nucleus RNA sequencing, we established the first molecular and cellular atlases of the adult spinal cord in both mouse and human. This work identified different organization of the dorsal and ventral regions of the spinal cord, revealed novel populations, and serve as an important references for our field. We've used similar techniques to probe cell-type specific changes in response to spinal cord injury, revealing spinocerebellar neurons that can regrow after contusion injury and neurons that support the recovery of locomotion with neuro-rehabilitation therapy.
How do specific spinal cord cell types contribute to behavior? We use mouse genetics, cell type specific viral manipulations, in vivo electrophysiology, and quantitative behavioral analysis to reveal how neuronal populations contribute to movement. We want to know how motor programs are encoded within spinal circuits, whether particular spinal populations contribute specific computations in motor control, and whether we can we relate cell-type connectivity, location, or other cellular features to function.
How are spinal cord cells incorporated into central nervous system-wide circuits for motor control? We want to know how descending pathways from the brain recruit specific spinal cord cells and circuits to enact movements. What are the roles of parallel descending pathways? We found a direct projection from the cerebellum to the spinal cord that is critical for motor behavior. Now, we want to know how spinal circuits can be dynamically recruited by descending pathways in different behavioral contexts.