Muscle Spindle Feedback Directs Locomotor Recovery and Circuit Reorganization after Spinal Cord Injury

• Published in: Cell Vol. 159; no. 7; pp. 1626 - 1639
• Main Authors: Takeoka, Aya, Vollenweider, Isabel, Courtine, Grégoire, Arber, Silvia
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 18.12.2014
• Subjects: animal injuries; Animals; Early Growth Response Protein 3 - genetics; Early Growth Response Protein 3 - metabolism; Feedback, Physiological; Locomotion; Mice; Muscle Spindles - physiology; muscles; mutants; neural networks; Neurons - physiology; spinal cord; Spinal Cord Injuries - metabolism; Spinal Cord Regeneration
• ISSN: 0092-8674; 1097-4172; 1097-4172
• DOI: 10.1016/j.cell.2014.11.019

Spinal cord injuries alter motor function by disconnecting neural circuits above and below the lesion, rendering sensory inputs a primary source of direct external drive to neuronal networks caudal to the injury. Here, we studied mice lacking functional muscle spindle feedback to determine the role of this sensory channel in gait control and locomotor recovery after spinal cord injury. High-resolution kinematic analysis of intact mutant mice revealed proficient execution in basic locomotor tasks but poor performance in a precision task. After injury, wild-type mice spontaneously recovered basic locomotor function, whereas mice with deficient muscle spindle feedback failed to regain control over the hindlimb on the lesioned side. Virus-mediated tracing demonstrated that mutant mice exhibit defective rearrangements of descending circuits projecting to deprived spinal segments during recovery. Our findings reveal an essential role for muscle spindle feedback in directing basic locomotor recovery and facilitating circuit reorganization after spinal cord injury. [Display omitted] •Muscle spindle afferents influence specific aspects of locomotor control•Muscle spindle feedback directs locomotor recovery after spinal cord injury•Descending detour circuit formation is facilitated by muscle spindle feedback Muscle spindle feedback to spinal neurons is essential for locomotor recovery after spinal cord injury, facilitating the formation of circuits from brainstem and spinal neurons that bridge the lesion.