Functional Local Proprioceptive Feedback Circuits Initiate and Maintain Locomotor Recovery after Spinal Cord Injury

Cell Rep. 2019 Apr 2;27(1):71-85.e3. doi: 10.1016/j.celrep.2019.03.010.


Somatosensory feedback from proprioceptive afferents (PAs) is essential for locomotor recovery after spinal cord injury. To determine where or when proprioception is required for locomotor recovery after injury, we established an intersectional genetic model for PA ablation with spatial and temporal confinement. We found that complete or spatially restricted PA ablation in intact mice differentially affects locomotor performance. Following incomplete spinal cord injury, PA ablation below but not above the lesion severely restricts locomotor recovery and descending circuit reorganization. Furthermore, ablation of PAs after behavioral recovery permanently reverts functional improvements, demonstrating their essential role for maintaining regained locomotor function despite the presence of reorganized descending circuits. In parallel to recovery, PAs undergo reorganization of activity-dependent synaptic connectivity to specific local spinal targets. Our study reveals that PAs interacting with local spinal circuits serve as a continued driving force to initiate and maintain locomotor output after injury.

Keywords: locomotion; mouse genetics; neuronal circuit reorganization; proprioception; somatosensory feedback; spinal cord injury; viral tracing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disease Models, Animal
  • Feedback, Sensory / physiology*
  • Female
  • Locomotion / physiology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Nerve Net / pathology
  • Nerve Net / physiopathology*
  • Nerve Regeneration
  • Proprioception / physiology*
  • Recovery of Function
  • Spinal Cord Injuries / pathology
  • Spinal Cord Injuries / physiopathology*
  • Spinal Cord Injuries / rehabilitation*