Neuroscience Area International School for Advanced Studies, Trieste, Italy.
J Neurophysiol. 2012 Dec;108(11):2977-90. doi: 10.1152/jn.00554.2012. Epub 2012 Sep 5.
A new stimulating protocol [fictive locomotion-induced stimulation (FListim)], consisting of intrinsically variable weak waveforms applied to a single dorsal root is very effective (though not optimal as it eventually wanes away) in activating the locomotor program of the isolated rat spinal cord. The present study explored whether combination of FListim with low doses of pharmacological agents that raise network excitability might further improve the functional outcome, using this in vitro model. FListim was applied together with N-methyl-d-aspartate (NMDA) + serotonin, while fictive locomotion (FL) was electrophysiologically recorded from lumbar ventral roots. Superimposing FListim on FL evoked by these neurochemicals persistently accelerated locomotor-like cycles to a set periodicity and modulated cycle amplitude depending on FListim rate. Trains of stereotyped rectangular pulses failed to replicate this phenomenon. The GABA(B) agonist baclofen dose dependently inhibited, in a reversible fashion, FL evoked by either FListim or square pulses. Sustained episodes of FL emerged when FListim was delivered, at an intensity subthreshold for FL, in conjunction with subthreshold pharmacological stimulation. Such an effect was, however, not found when high potassium solution instead of NMDA + serotonin was used. These results suggest that the combined action of subthreshold FListim (e.g., via epidural stimulation) and neurochemicals should be tested in vivo to improve locomotor rehabilitation after injury. In fact, reactivation of spinal locomotor circuits by conventional electrical stimulation of afferent fibers is difficult, while pharmacological activation of spinal networks is clinically impracticable due to concurrent unwanted effects. We speculate that associating subthreshold chemical and electrical inputs might decrease side effects when attempting to evoke human locomotor patterns.
一种新的刺激方案[虚构运动诱导刺激（FListim）]，由应用于单个背根的内在可变弱波组成，在激活分离的大鼠脊髓的运动程序方面非常有效（尽管不是最佳效果，因为它最终会减弱）。本研究使用这种体外模型探索了 FListim 与提高网络兴奋性的低剂量药物组合是否可以进一步改善功能结果。FListim 与 N-甲基-D-天冬氨酸（NMDA）+ 5-羟色胺一起应用，同时从腰神经根记录虚构运动（FL）的电生理记录。将 FListim 叠加在这些神经化学物质引起的 FL 上，会持续将运动样周期加速到设定的周期性，并根据 FListim 速率调制周期幅度。规则矩形脉冲的序列无法复制这种现象。GABA（B）激动剂巴氯芬以可逆转的方式抑制由 FListim 或方波引起的 FL，抑制程度取决于 FListim 的强度。当 FListim 以低于 FL 的强度与亚阈值药物刺激一起传递时，会出现持续的 FL 发作。然而，当使用高钾溶液代替 NMDA+5-羟色胺时，并未发现这种效果。这些结果表明，应该在体内测试亚阈值 FListim（例如通过硬膜外刺激）与神经化学物质的联合作用，以改善损伤后的运动康复。事实上，由于并发的不良反应，通过传入纤维的常规电刺激重新激活脊髓运动回路是困难的，而脊髓网络的药物激活在临床上是不可行的。我们推测，当试图诱发人类运动模式时，将亚阈值化学和电输入结合起来可能会降低副作用。
