Extended Data Fig 9: Intersectional genetics to target specific pathways and probe their function.

a, Optogenetic silencing of the corticospinal tract in the lumbar spinal cord. Step 1: Timeline detailing key experiments. Step 2: Schematic illustration of the experimental procedures to target corticospinal tract neurons with synaptic projections to the lumbar spinal cord with Jaws. Step 3: Mice are walking freely when the photostimulation is suddenly turned on. Step 4: A series of 78 gait parameters (see Supplementary Table 1) calculated from the kinematic recordings are submitted to a PC analysis. Each dot represents the mean and SEM values of many gait cycles (n > 10 per mouse) are shown in the new denoised space defined by PC1 and PC2. Step 5: Factors loadings of individual parameters on PC1 (correlation between PC1 and each variable). Step 6: Functional clusters of highly correlated parameters were extracted from PC1 loadings representing gait parameters that describe differences between groups the most. Parameteres relating to paw dragging and balance explained a large variance of the gait cycles, therefore indicating it best describes differences between groups. Step 7: Post-mortem verification of Jaws expression. Photographs show the robust expession of Jaws in the lumbar spinal cord, as well as in neurons located in the injected region of the primary motor cortex. b, Optogenetic siliencing of the reticulospinal tract in the lumbar spinal cord. Step 1: Timeline detailing key experiments. Step 2: Schematic illustration of the experimental procedures to target reticulospinal tract neurons with synaptic projections to the lumbar spinal cord with Jaws. Step 3: Mice are walking freely when the photostimulation is suddenly turned on. Step 4: A series of 78 gait parameters (see Supplementary Table 1) calculated from the kinematic recordings are submitted to a PC analysis. Each dot represents the mean and SEM values of many gait cycles (n > 10 pre mouse) are shown in the new denoised space defined by PC1 and PC2. Step 5: Factors loadings of individual parameters on PC1 (correlation between PC1 and each variable). Step 6: Functional clusters of highly correlated parameters were extracted from PC1 loadings representing gait parameters that describe differences between groups the most. Parameteres relating to paw dragging and step height explained a large variance of the gait cycles, therefore indicating it best describes differences between groups. Step 7: Post-moterm verification of Jaws expression. Photographs show the robust expession of Jaws in the lumbar spinal cord, as well as in neurons located in the ventral gigantocellular nucleus.