Coordinated neurostimulation promotes circuit rewiring and unlocks recovery after spinal cord injury

Functional recovery after incomplete spinal cord injury depends on the effective rewiring of neuronal circuits. Here, we show that selective chemogenetic activation of either corticospinal projection neurons or intraspinal relay neurons alone led to anatomically restricted plasticity and little functional recovery. In contrast, coordinated stimulation of both supraspinal centers and spinal relay stations resulted in marked and circuit-specific enhancement of neuronal rewiring, shortened EMG latencies, and improved locomotor recovery. Functional recovery after spinal cord injury is guided by the formation of new spinal detour circuits. The authors show that the formation of these circuits is enhanced by targeted chemogenetic stimulation of supraspinal and spinal neuron populations. Supraspinal and spinal coordinated stimulation potentiated behavioral recovery.