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

• Published in: Cell reports (Cambridge) Vol. 27; no. 1; pp. 71 - 85.e3
• Main Authors: Takeoka, Aya, Arber, Silvia
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 02.04.2019; Elsevier
• Subjects: locomotion; mouse genetics; neuronal circuit reorganization; proprioception; somatosensory feedback; spinal cord injury; viral tracing; spinal cord injury; somatosensory feedback; locomotion; mouse genetics; proprioception; viral tracing; neuronal circuit reorganization
• ISSN: 2211-1247; 2211-1247
• 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. [Display omitted] •Proprioceptive feedback below the lesion drives spontaneous locomotor recovery•Maintaining motor function regained after injury requires proprioceptive feedback•Descending circuit reorganization requires proprioceptive feedback below the injury•Proprioceptive afferents undergo activity-dependent local connectivity changes Takeoka and Arber examined the spatial and temporal requirements of proprioceptive feedback in recovery after spinal cord injury. They reveal an indispensable role for proprioceptive afferents below the injury in the initiation and maintenance of locomotor recovery. The activity of proprioceptive afferents contributes to local and descending circuit rearrangements that parallel recovery.