Computation and Neural Systems, California Institute of Technology, Pasadena, California.
Department of Integrative Biology and Physiology, University of California, Los Angeles, California.
J Neurophysiol. 2021 Sep 1;126(3):957-966. doi: 10.1152/jn.00422.2020. Epub 2021 Aug 18.
Having observed that electrical spinal cord stimulation and training enabled four patients with paraplegia with motor complete paralysis to regain voluntary leg movement, the underlying mechanisms involved in forming the newly established supraspinal-spinal functional connectivity have become of great interest. van den Brand et al. ( 336: 1182-1185, 2012) subsequently, demonstrated the recovery, in response to spinal electro-neuromodulation and locomotor training, of voluntary stepping of the lower limbs in rats that received a lesion that is assumed to eliminate all long-descending cortical axons that project to lumbosacral segments. Here, we used a similar spinal lesion in rats to eliminate long-descending axons to determine whether a novel, trained motor behavior triggered by a unique auditory cue learned before a spinal lesion, could recover after the lesion. Hindlimb stepping recovered 1 mo after the spinal injury, but only after 2 mo, the novel and unique audio-triggered behavior was recovered, meaning that not only was a novel connectivity formed but also further evidence suggested that this highly unique behavioral response was independent of the recovery of the circuitry that generated stepping. The unique features of the newly formed supraspinal-spinal connections that mediated the recovery of the trained behavior is consistent with a guidance mechanism(s) that are highly use dependent. Electrical spinal cord stimulation has enabled patients with paraplegia to regain voluntary leg movement, and so the underlying mechanisms involved in this recovery are of great interest. Here, we demonstrate in rodents the recovery of trained motor behavior after a spinal lesion. Rodents were trained to kick their right hindlimb in response to an auditory cue. This behavior recovered 2 mo after the paralyzing spinal cord injury but only with the assistance of electrical spinal cord stimulation.
观察到电脊髓刺激和训练使 4 名完全性截瘫的脊髓损伤患者恢复了自主腿部运动后,新建立的脊髓上-脊髓功能连接的潜在机制变得非常有趣。van den Brand 等人随后证明,在接受假定消除所有投射到腰骶段的长下行皮质轴突的损伤的大鼠中,脊髓电神经调节和运动训练恢复了下肢的自主踏步。在这里,我们使用类似的大鼠脊髓损伤来消除长下行轴突,以确定在脊髓损伤前学习的独特听觉提示引发的新的训练运动行为是否可以在损伤后恢复。损伤后 1 个月,后肢踏步恢复,但仅在损伤后 2 个月,新的独特听觉触发行为恢复,这意味着不仅形成了新的连接,而且进一步的证据表明,这种高度独特的行为反应独立于产生踏步的电路的恢复。介导训练行为恢复的新形成的脊髓上-脊髓连接的独特特征与高度依赖使用的导向机制一致。电脊髓刺激使截瘫患者恢复了自主腿部运动,因此这种恢复所涉及的潜在机制非常有趣。在这里,我们在啮齿动物中证明了脊髓损伤后的训练运动行为的恢复。啮齿动物接受训练,以响应听觉提示踢他们的右后肢。这种行为在瘫痪性脊髓损伤后 2 个月恢复,但仅在电脊髓刺激的辅助下恢复。