TY - JOUR T1 - Persistent beneficial impact of H-reflex conditioning in spinal cord-injured rats. JF - J Neurophysiol Y1 - 2014 A1 - Yi Chen A1 - Lu Chen A1 - Wang, Yu A1 - Jonathan Wolpaw A1 - Xiang Yang Chen KW - H-reflex conditioning KW - Learning KW - Locomotion KW - Memory KW - Motor control KW - Rehabilitation KW - spinal cord injury KW - spinal cord plasticity AB -

Operant conditioning of a spinal cord reflex can improve locomotion in rats and humans with incomplete spinal cord injury. This study examined the persistence of its beneficial effects. In rats in which a right lateral column contusion injury had produced asymmetric locomotion, up-conditioning of the right soleus H-reflex eliminated the asymmetry while down-conditioning had no effect. After the 50-day conditioning period ended, the H-reflex was monitored for 100 [±9 (SD)] (range 79-108) more days and locomotion was then reevaluated. After conditioning ended in up-conditioned rats, the H-reflex continued to increase, and locomotion continued to improve. In down-conditioned rats, the H-reflex decrease gradually disappeared after conditioning ended, and locomotion at the end of data collection remained as impaired as it had been before and immediately after down-conditioning. The persistence (and further progression) of H-reflex increase but not H-reflex decrease in these spinal cord-injured rats is consistent with the fact that up-conditioning improved their locomotion while down-conditioning did not. That is, even after up-conditioning ended, the up-conditioned H-reflex pathway remained adaptive because it improved locomotion. The persistence and further enhancement of the locomotor improvement indicates that spinal reflex conditioning protocols might supplement current therapies and enhance neurorehabilitation. They may be especially useful when significant spinal cord regeneration becomes possible and precise methods for retraining the regenerated spinal cord are needed.

VL - 112 UR - http://www.ncbi.nlm.nih.gov/pubmed/25143542 IS - 10 ER - TY - JOUR T1 - H-reflex down-conditioning greatly increases the number of identifiable GABAergic interneurons in rat ventral horn. JF - Neuroscience letters Y1 - 2009 A1 - Wang, Yu A1 - Pillai, Shreejith A1 - Jonathan Wolpaw A1 - Xiang Yang Chen KW - activity-dependent plasticity KW - GABAergic interneurons KW - H-reflex conditioning KW - learning and memory KW - Motor control KW - Spinal Cord AB - H-reflex down-conditioning increases GABAergic terminals on spinal cord motoneurons. To explore the origins of these terminals, we studied the numbers and distributions of spinal cord GABAergic interneurons. The number of identifiable GABAergic interneurons in the ventral horn was 78% greater in rats in which down-conditioning was successful than in naive rats or rats in which down-conditioning failed. No increase occurred in other spinal lamina or on the contralateral side. This finding supports the hypothesis that the corticospinal tract influence that induces the motoneuron plasticity underlying down-conditioning reaches the motoneuron through GABAergic interneurons in the ventral horn. VL - 452 UR - http://www.ncbi.nlm.nih.gov/pubmed/19383426 ER - TY - JOUR T1 - Effects of H-reflex up-conditioning on GABAergic terminals on rat soleus motoneurons. JF - The European journal of neuroscience Y1 - 2008 A1 - Pillai, Shreejith A1 - Wang, Yu A1 - Jonathan Wolpaw A1 - Xiang Yang Chen KW - activity-dependent plasticity KW - Learning KW - Memory KW - Motor control KW - Spinal Cord AB - To explore the role of spinal cord plasticity in motor learning, we evaluated the effects of H-reflex operant conditioning on GABAergic input to rat spinal motoneurons. Previous work indicated that down-conditioning of soleus H-reflex increases GABAergic input to soleus motoneurons. This study explored the effect of H-reflex up-conditioning on GABAergic input. Of nine rats exposed to H-reflex up-conditioning, up-conditioning was successful (H-reflex increase >or= 20%) in seven and failed (change < 20%) in two. These rats and eight naive control (i.e. unconditioned) rats were injected with cholera toxin subunit B-conjugated Alexa fluor 488 into the soleus muscle to retrogradely label soleus motoneurons. Sections containing soleus motoneurons were processed for GAD(67) [one of the two principal forms of the GABA-synthesizing enzyme glutamic acid decarboxylase (GAD)] with an ABC-peroxidase system. Two blinded independent raters counted and measured GABAergic terminals on these motoneurons. Unlike successful down-conditioning, which greatly increased the number of identifiable GABAergic terminals on the motoneurons, up-conditioning did not significantly change GABAergic terminal number. Successful up-conditioning did produce slight but statistically significant increases in GABAergic terminal diameter and soma coverage. These results are consistent with other data indicating that up- and down-conditioning are not mirror images of each other, but rather have different mechanisms. Although the marked changes in GABAergic terminals with down-conditioning probably contribute to H-reflex decrease, the modest changes in GABAergic terminals associated with up-conditioning may be compensatory or reactive plasticity, rather than the plasticity responsible for H-reflex increase. As a variety of spinal and supraspinal GABAergic neurons innervate motoneurons, the changes found with up-conditioning may be in terminals other than those affected in successful down-conditioning. VL - 28 UR - http://www.ncbi.nlm.nih.gov/pubmed/18657184 ER - TY - JOUR T1 - Motor learning changes GABAergic terminals on spinal motoneurons in normal rats. JF - The European journal of neuroscience Y1 - 2006 A1 - Wang, Yu A1 - Pillai, Shreejith A1 - Jonathan Wolpaw A1 - Xiang Yang Chen KW - activity-dependent plasticity KW - GABA KW - H-Reflex KW - Memory KW - Motor control KW - Spinal Cord AB - The role of spinal cord plasticity in motor learning is largely unknown. This study explored the effects of H-reflex operant conditioning, a simple model of motor learning, on GABAergic input to spinal motoneurons in rats. Soleus motoneurons were labeled by retrograde transport of a fluorescent tracer and GABAergic terminals on them were identified by glutamic acid decarboxylase (GAD)67 immunoreactivity. Three groups were studied: (i) rats in which down-conditioning had reduced the H-reflex (successful HRdown rats); (ii) rats in which down-conditioning had not reduced the H-reflex (unsuccessful HRdown rats) and (iii) unconditioned (naive) rats. The number, size and GAD density of GABAergic terminals, and their coverage of the motoneuron, were significantly greater in successful HRdown rats than in unsuccessful HRdown or naive rats. It is likely that these differences are due to modifications in terminals from spinal interneurons in lamina VI-VII and that the increased terminal number, size, GAD density and coverage in successful HRdown rats reflect and convey a corticospinal tract influence that changes motoneuron firing threshold and thereby decreases the H-reflex. GABAergic terminals in spinal cord change after spinal cord transection. The present results demonstrate that such spinal cord plasticity also occurs in intact rats in the course of motor learning and suggest that this plasticity contributes to skill acquisition. VL - 23 UR - http://www.ncbi.nlm.nih.gov/pubmed/16420424 ER -