A Surviving Intact Branch Stabilizes Remaining Axon Architecture after Injury as Revealed by In Vivo Imaging in the Mouse Spinal Cord

•Acute axon degeneration is bidirectional but exhibits an unexpected asymmetry•Injury location relative to a branch point impacts degeneration and regeneration•A surviving intact branch suppresses further degeneration and regeneration•Regenerating axons exhibit dynamic regeneration, pruning and remodeling over time

SummaryThe complex morphology of axons presents a challenge in understanding axonal responses to injury and disease. By in vivo two-photon imaging of spinal dorsal column sensory axons, we systematically examined the effect of injury location relative to the main bifurcation point on axon degeneration and regeneration following highly localized laser injuries. Retrograde but not anterograde degeneration was strongly blocked at the bifurcation point at both the acute and subacute phases. Eliminating either the ascending or descending branch led to a poor regenerative response, while eliminating both led to a strong regenerative response. Thus, a surviving intact branch suppresses both retrograde degeneration and regeneration of the injured branch, thereby preserving the remaining axon architecture. Regenerating axons exhibited a dynamic pattern with alternating phases of regeneration and pruning over a chronic period. In vivo imaging continues to reveal new insights on axonal responses to injury in the mammalian spinal cord.