Song Weiguo, Martin John H
Department of Molecular, Cellular, and Biomedical Sciences, Center for Discovery and Innovation, City University of New York School of Medicine, New York, NY, United States.
Institute of Bioelectronic Medicine, Feinstein Institutes for Medical Research, Manhasset, NY, United States.
Front Neurosci. 2022 Apr 25;16:856948. doi: 10.3389/fnins.2022.856948. eCollection 2022.
Trans-spinal direct current stimulation (tsDCS) is a neuromodulatory approach to augment spinal cord activity to improve function after neurological disease and injury. Little is known about the mechanisms underlying tsDCS actions on the motor system. The purpose of this study is to determine the role for a persistent inward current (PIC)-like response in motoneurons in mediating tsDCS actions. We recorded single motor units from the extensor and flexor carpi radialis muscles in healthy sedated rats and measured unit activity changes produced by cervical enlargement cathodal and anodal tsDCS (c-tsDCS; a-tsDCS). Both c-tsDCS and a-tsDCS immediately increased spontaneous motor unit firing during stimulation. After c-tsDCS was stopped, spontaneous firing persisted for a substantial period (165 ± 5s), yet after a-tsDCS activity shortly returned to baseline (27 ± 7s). Administration of the L-type calcium channel blocker Nimodipine reduced spontaneous motor unit firing during c-tsDCS and blocked the persistent response. By contrast, Nimodipine did not change unit firing during a-tsDCS but the short persistent response was blocked. Computer simulation using a two-compartment neuronal model replicated the main experimental observations: larger and more persistent responses during and after c-tsDCS than a-tsDCS. Using reduced Ca conductance to model Nimodipine action, a reduced response during c-tsDCS and elimination of the persistent response was observed. Our experimental findings, supported by computer simulation, show that c-tsDCS can target Ca conductances to augment motoneuron activity. As tsDCS is well-tolerated in humans, this knowledge informs therapeutic treatment strategies to achieve rehabilitation goals after injury; in particular, to increase muscle force.
经脊髓直流电刺激（tsDCS）是一种神经调节方法，可增强脊髓活动，以改善神经疾病和损伤后的功能。目前对于tsDCS作用于运动系统的潜在机制知之甚少。本研究的目的是确定运动神经元中类似持续性内向电流（PIC）的反应在介导tsDCS作用中的作用。我们在健康的镇静大鼠中记录了桡侧腕伸肌和桡侧腕屈肌的单个运动单位，并测量了颈膨大阴极和阳极tsDCS（c-tsDCS；a-tsDCS）产生的单位活动变化。c-tsDCS和a-tsDCS在刺激期间均立即增加了自发运动单位放电。c-tsDCS停止后，自发放电持续了相当长的一段时间（165±5秒），而a-tsDCS活动后不久就恢复到基线（27±7秒）。给予L型钙通道阻滞剂尼莫地平可减少c-tsDCS期间的自发运动单位放电，并阻断持续性反应。相比之下，尼莫地平在a-tsDCS期间并未改变单位放电，但短暂的持续性反应被阻断。使用双室神经元模型进行的计算机模拟复制了主要实验观察结果：c-tsDCS期间及之后的反应比a-tsDCS更大且更持久。使用降低的钙电导来模拟尼莫地平的作用，观察到c-tsDCS期间反应降低且持续性反应消除。我们的实验结果得到计算机模拟的支持，表明c-tsDCS可以靶向钙电导以增强运动神经元活动。由于tsDCS在人类中耐受性良好，这一知识为实现损伤后康复目标的治疗策略提供了依据；特别是增加肌肉力量。
