Department of Physiology, Section of Neurology, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.
J Neurophysiol. 2011 Jun;105(6):2818-29. doi: 10.1152/jn.00917.2010. Epub 2011 Mar 30.
Previous studies of the in vitro neonatal rat brain stem-spinal cord showed that propriospinal relays contribute to descending transmission of a supraspinal command signal that is capable of activating locomotion. Using the same preparation, the present series examines whether enhanced excitation of thoracic propriospinal neurons facilitates propagation of the locomotor command signal in the lesioned spinal cord. First, we identified neurotransmitters contributing to normal endogenous propriospinal transmission of the locomotor command signal by testing the effect of receptor antagonists applied to cervicothoracic segments during brain stem-induced locomotor-like activity. Spinal cords were either intact or contained staggered bilateral hemisections located at right T1/T2 and left T10/T11 junctions designed to abolish direct long-projecting bulbospinal axons. Serotonergic, noradrenergic, dopaminergic, and glutamatergic, but not cholinergic, receptor antagonists blocked locomotor-like activity. Approximately 73% of preparations with staggered bilateral hemisections failed to generate locomotor-like activity in response to electrical stimulation of the brain stem alone; such preparations were used to test the effect of neuroactive substances applied to thoracic segments (bath barriers placed at T3 and T9) during brain stem stimulation. The percentage of preparations developing locomotor-like activity was as follows: 5-HT (43%), 5-HT/N-methyl-D-aspartate (NMDA; 33%), quipazine (42%), 8-hydroxy-2-(di-n-propylamino)tetralin (20%), methoxamine (45%), and elevated bath K(+) concentration (29%). Combined norepinephrine and dopamine increased the success rate (67%) compared with the use of either agent alone (4 and 7%, respectively). NMDA, Mg(2+) ion removal, clonidine, and acetylcholine were ineffective. The results provide proof of principle that artificial excitation of thoracic propriospinal neurons can improve supraspinal control over hindlimb locomotor networks in the lesioned spinal cord.
先前研究体外新生大鼠脑干-脊髓显示，固有脊髓中继有助于增强上位命令信号的下行传递，从而激活运动。本研究采用相同的制备方法，检验增强胸段固有脊髓神经元的兴奋是否有助于损伤脊髓中运动命令信号的传播。首先，我们通过测试受体拮抗剂对脑干诱导的类似运动活动期间颈胸段的影响，确定了有助于正常内源性运动命令信号固有脊髓传递的神经递质。脊髓完整或包含位于右侧 T1/T2 和左侧 T10/T11 交界处的交错双侧半切，旨在消除直接长投射的球脊髓轴突。5-羟色胺能、去甲肾上腺素能、多巴胺能和谷氨酸能受体拮抗剂阻断了类似运动的活动，但胆碱能受体拮抗剂没有。大约 73%的交错双侧半切制备物不能对单独的脑干电刺激产生类似运动的活动；这些制备物用于测试在脑干刺激期间应用于胸段的神经活性物质（放置在 T3 和 T9 的浴障）的影响。产生类似运动活动的制备物百分比如下：5-HT（43%）、5-HT/N-甲基-D-天冬氨酸（NMDA；33%）、quipazine（42%）、8-羟基-2-（二正丙基氨基）四氢萘（20%）、甲氧胺（45%）和升高的浴液 K+浓度（29%）。与单独使用任一药物（分别为 4%和 7%）相比，联合使用去甲肾上腺素和多巴胺提高了成功率（67%）。NMDA、Mg2+离子去除、可乐定和乙酰胆碱无效。结果提供了一个原理证明，即人工刺激胸段固有脊髓神经元可以改善损伤脊髓中上位对后肢运动网络的控制。
