A severe contusion of thoracic segments disrupts the motor-circuit communication matrix linking the brain and the spinal cord. Electrochemical stimulation applied over lumbar segments restored this communication, which enabled volitional control of leg movements in rodents and humans with motor complete paralysis. However, the circuit-level mechanisms through which the cortical drive regains functional access to the spinal circuits controlling leg movements during electrochemical stimulation remain poorly understood. Using mice expressing light-sensitive channels in cortical projection neurons, we first showed that electrochemical stimulation enabled the hindlimb motor cortex to regain a graded control over hindlimb locomotor movements in otherwise paralyzed animals. Using virus-mediated tract tracing and circuit-specific inactivation techniques, we found that after injury the cortical drive is rerouted through glutamatergic reticular neurons with residual projections below the injury. Robot-assisted gait training enabled by electrochemical stimulation promoted an extensive reorganization of these pathways. We found a robust growth of motor cortex projections into the reticular formation, and a substantial sprouting of residual reticulospinal axons into specific regions of the spinal cord below the injury. We established causal relationships between this anatomical reorganization and the recovery of voluntary leg motor control in response to gait rehabilitation. These results illustrate the remarkable capability of neural pathways to reorganize in order to mediate motor recovery, even after the most severe types of spinal cord injury.
*L. ASBOTH, Q. BARRAUD, L. FRIEDLI, J. BEAUPARLANT, C. MARTINEZ-GONZALEZ, S. ANIL, G. PIDPRUZHNYKOVA, E. REY, L. BAUD, J. KREIDER, M. ANDERSON, J. VON ZITZEWITZ, G. COURTINE;
Swiss Federal Inst. of Technol., Lausanne, Switzerland
L. Asboth: None. Q. Barraud: None. L. Friedli: None. J. Beauparlant: None. C. Martinez-Gonzalez: None. S. Anil: None. G. Pidpruzhnykova: None. E. Rey: None. L. Baud: None. J. Kreider: None. M. Anderson: None. J. von Zitzewitz: None. G. Courtine: None.