Duru Paul O, Tillakaratne Niranjala J K, Kim Jung A, Zhong Hui, Stauber Stacey M, Pham Trinh T, Xiao Mei S, Edgerton V Reggie, Roy Roland R
Department of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, California.
Brain Research Institute, University of California, Los Angeles, Los Angeles, California.
J Neurosci Res. 2015 Aug;93(8):1229-39. doi: 10.1002/jnr.23579. Epub 2015 Mar 18.
The neural networks that generate stepping in complete spinal adult rats remain poorly defined. To address this problem, we used c-fos (an activity-dependent marker) to identify active interneurons and motoneurons in the lumbar spinal cord of adult spinal rats during a 30-min bout of bipedal stepping. Spinal rats were either step trained (30 min/day, 3 days/week, for 7.5 weeks) or not step trained. Stepping was enabled by epidural stimulation and the administration of the serotonergic agonists quipazine and 8-OHDPAT. A third group of spinal rats served as untreated (no stimulation, drugs, or stepping) controls. The numbers of activated cholinergic central canal cluster cells and partition neurons were higher in both step-trained and nontrained rats than in untreated rats and were higher in nontrained than in step-trained rats. The latter finding suggests that daily treatment with epidural stimulation plus serotonergic agonist treatment without step training enhances the excitability of a broader cholinergic interneuronal population than does step training. The numbers of activated interneurons in laminae II-VI of lumbar cross-sections were higher in both step-trained and nontrained rats than in untreated rats, and they were highest in step-trained rats. This finding suggests that this population of interneurons is responsive to epidural stimulation plus serotonergic treatment and that load-bearing induced when stepping has an additive effect. The numbers of activated motoneurons of all size categories were higher in the step-trained group than in the other two groups, reflecting a strong effect of loading on motoneuron recruitment. In general, these results indicate that the spinal networks for locomotion are similar with and without brain input.
We identified neurons within the spinal cord networks that are activated during assisted stepping in paraplegic rats. We stimulated the spinal cord and administered a drug to help the rats step. One group was trained to step and another was not trained. We observed a lower percentage of activated neurons in specific spinal cord regions in trained rats than in nontrained rats after a 1-hr stepping bout, suggesting that step training reduces activation of some types of spinal neurons. This observation indicates that training makes the spinal networks more efficient and suggests a "learning" phenomenon in the spinal cord without any brain input.
在成年完全脊髓损伤大鼠中产生踏步运动的神经网络仍未完全明确。为了解决这个问题,我们使用c-fos(一种活动依赖性标记物)来识别成年脊髓损伤大鼠在30分钟双足踏步运动期间腰段脊髓中活跃的中间神经元和运动神经元。脊髓损伤大鼠分为接受踏步训练组(每天30分钟,每周3天,共7.5周)和未接受踏步训练组。通过硬膜外刺激以及给予血清素能激动剂喹哌嗪和8-羟基二苯丙氨酸来诱发踏步运动。第三组脊髓损伤大鼠作为未处理(无刺激、无药物、无踏步运动)对照组。在接受踏步训练的大鼠和未接受训练的大鼠中,被激活的胆碱能中央管簇细胞和分隔神经元的数量均高于未处理的大鼠,且未接受训练的大鼠中的数量高于接受踏步训练的大鼠。后一发现表明,在不进行踏步训练的情况下,每日进行硬膜外刺激加血清素能激动剂治疗比踏步训练能增强更广泛的胆碱能中间神经元群体的兴奋性。在腰段横切面的II-VI层中,接受踏步训练的大鼠和未接受训练的大鼠中被激活的中间神经元数量均高于未处理的大鼠,且在接受踏步训练的大鼠中数量最多。这一发现表明,这群中间神经元对硬膜外刺激加血清素能治疗有反应,且踏步运动时产生的负重具有累加效应。所有大小类别的被激活运动神经元数量在接受踏步训练的组中高于其他两组,这反映了负重对运动神经元募集的强烈影响。总体而言,这些结果表明,有无脑输入时,脊髓运动网络是相似的。
我们识别出了截瘫大鼠在辅助踏步运动期间脊髓网络中被激活的神经元。我们刺激脊髓并给予药物帮助大鼠踏步。一组接受踏步训练,另一组未接受训练。在1小时的踏步运动后,我们观察到接受训练的大鼠特定脊髓区域中被激活神经元的百分比低于未接受训练的大鼠,这表明踏步训练会降低某些类型脊髓神经元的激活。这一观察结果表明训练使脊髓网络更高效,并提示在没有任何脑输入的情况下脊髓中存在“学习”现象。