Biozentrum, Department of Cell Biology, University of Basel, 4056 Basel, Switzerland; Friedrich Miescher Institute for Biomedical Research, 4058 Basel, Switzerland.
Brain Mind Institute and Centre for Neuroprosthetics, Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.
Cell. 2014 Dec 18;159(7):1626-39. 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.
脊髓损伤通过切断损伤上下的神经回路来改变运动功能,使感觉输入成为损伤以下神经元网络的直接外部驱动的主要来源。在这里,我们研究了缺乏功能性肌梭反馈的小鼠,以确定这种感觉通道在步态控制和脊髓损伤后运动功能恢复中的作用。对完整突变小鼠的高分辨率运动学分析显示,它们在基本运动任务中执行能力良好,但在精细任务中表现不佳。损伤后,野生型小鼠自发恢复了基本的运动功能,而缺乏肌梭反馈的小鼠则无法恢复损伤侧后肢的控制。病毒介导的追踪表明,在恢复过程中,突变小鼠表现出投射到剥夺脊髓节段的下行回路的缺陷性重排。我们的研究结果揭示了肌梭反馈在指导基本运动恢复和促进脊髓损伤后回路重组中的重要作用。