Brain-wide analysis of the supraspinal connectome reveals anatomical correlates to functional recovery after spinal injury

The supraspinal connectome is essential for normal behavior and homeostasis and consists of numerous sensory, motor, and autonomic projections from brain to spinal cord. Study of supraspinal control and its restoration after damage has focused mostly on a handful of major populations that carry motor commands, with only limited consideration of dozens more that provide autonomic or crucial motor modulation. We now provide an experimental platform and associated web-based resource to rapidly profile the entire supraspinal mesoconnectome in adult mice. Optimized viral labeling, 3D imaging, and registration to a mouse digital neuroanatomical atlas assigned tens of thousands of supraspinal neurons to more than 60 identified regions. We demonstrate the approach’s ability to clarify essential points of topographic mapping between spinal levels, to measure population-specific sensitivity to spinal injury, and to resolve previously unexplained variability in functional recovery. This work will spur progress by broadening understanding and enabling analyses of essential but understudied supraspinal populations.