Mahrous Amr A, Mousa Mohamed H, Elbasiouny Sherif M
Department of Neuroscience, Cell Biology, and Physiology, Boonshoft School of Medicine and College of Science and Mathematics, Wright State University, Dayton, OH, United States.
Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States.
Front Cell Neurosci. 2019 Aug 9;13:359. doi: 10.3389/fncel.2019.00359. eCollection 2019.
Electrical stimulation of the spinal cord is a promising rehabilitation intervention to restore/augment motor function after spinal cord injury (SCI). Combining sensory feedback with stimulation of remaining motor circuits has been shown to be a prerequisite for the functional improvement of SCI patients. However, little is known about the cellular mechanisms potentially underlying this functional benefit in the injured spinal cord. Here, we combine computer simulations with an isolated whole-tissue adult mouse spinal cord preparation to examine synaptic, cellular, and system potentials measured from single motoneurons and ventral roots. The stimulation protocol included separate and combined activation of the sensory inputs (evoked by dorsal root stimulation) and motor inputs (evoked by stimulation of spinal cord tissue) at different frequencies, intensities, and neuromodulatory states. Our data show that, while sensory inputs exhibit short-term depression in response to a train of stimulation, motor inputs exhibit short-term facilitation. However, the concurrent activation of both inputs elicits a stronger and steadier motor output. This effect is enhanced by the application of pharmacological neuromodulators. Furthermore, sensorimotor excitatory postsynaptic potentials (EPSPs) summate sublinearly (i.e., their combination produces an excitatory potential smaller than the sum of the excitatory potentials they would individually produce). However, ventral root compound action potentials (CoAPs) summate supralinearly generating much higher outputs. Computer simulations revealed that the contrasting summation and disproportionality in plasticity between the excitatory postsynaptic potentials (EPSPs) and CoAPs result from the motoneuronal firing threshold acting as an amplitude-selective filter. Together, these results provide the mechanistic basis for the cellular processes contributing to the generation of steady motor outputs using spinal stimulation. This data has great potential to guide the design of more effective stimulation protocols in SCI patients.
脊髓电刺激是一种很有前景的康复干预手段，用于恢复/增强脊髓损伤（SCI）后的运动功能。将感觉反馈与剩余运动回路的刺激相结合已被证明是SCI患者功能改善的先决条件。然而，对于损伤脊髓中这种功能益处潜在的细胞机制却知之甚少。在这里，我们将计算机模拟与分离的成年小鼠全组织脊髓标本相结合，以检查从单个运动神经元和腹根测量到的突触、细胞和系统电位。刺激方案包括在不同频率、强度和神经调节状态下分别和联合激活感觉输入（由背根刺激诱发）和运动输入（由脊髓组织刺激诱发）。我们的数据表明，虽然感觉输入在一系列刺激下表现出短期抑制，但运动输入表现出短期易化。然而，两种输入的同时激活会引发更强且更稳定的运动输出。应用药理学神经调节剂可增强这种效应。此外，感觉运动兴奋性突触后电位（EPSP）呈亚线性总和（即它们的组合产生的兴奋性电位小于它们单独产生的兴奋性电位之和）。然而，腹根复合动作电位（CoAP）呈超线性总和，产生更高的输出。计算机模拟显示，兴奋性突触后电位（EPSP）和CoAP之间在可塑性方面的对比性总和及不成比例是由运动神经元放电阈值作为幅度选择性滤波器所致。总之，这些结果为利用脊髓刺激产生稳定运动输出的细胞过程提供了机制基础。这些数据对于指导设计更有效的SCI患者刺激方案具有巨大潜力。
