03911nas a2200361   4500008004100000022001400041245007800055210006900133260001300202300001400215490000800229520287700237653001203114653001303126653002503139653001003164653002603174653001303200653001303213653000903226653001803235653002403253653000903277653002503286653001603311100001303327700001303340700001303353700002103366700002203387700002403409856011603433       2024                        eng d  a1469-779300aMotor learning changes the axon initial segment of the spinal motoneuron.0 aMotor learning changes the axon initial segment of the spinal mo  c2024 May  a2107-21260 v6023 a<p>We are studying the mechanisms of H-reflex operant conditioning, a simple form of learning. Modelling studies in the literature and our previous data suggested that changes in the axon initial segment (AIS) might contribute. To explore this, we used blinded quantitative histological and immunohistochemical methods to study in adult rats the impact of H-reflex conditioning on the AIS of the spinal motoneuron that produces the reflex. Successful, but not unsuccessful, H-reflex up-conditioning was associated with greater AIS length and distance from soma; greater length correlated with greater H-reflex increase. Modelling studies in the literature suggest that these increases may increase motoneuron excitability, supporting the hypothesis that they may contribute to H-reflex increase. Up-conditioning did not affect AIS ankyrin G (AnkG) immunoreactivity (IR), p-p38 protein kinase IR, or GABAergic terminals. Successful, but not unsuccessful, H-reflex down-conditioning was associated with more GABAergic terminals on the AIS, weaker AnkG-IR, and stronger p-p38-IR. More GABAergic terminals and weaker AnkG-IR correlated with greater H-reflex decrease. These changes might potentially contribute to the positive shift in motoneuron firing threshold underlying H-reflex decrease; they are consistent with modelling suggesting that sodium channel change may be responsible. H-reflex down-conditioning did not affect AIS dimensions. This evidence that AIS plasticity is associated with and might contribute to H-reflex conditioning adds to evidence that motor learning involves both spinal and brain plasticity, and both neuronal and synaptic plasticity. AIS properties of spinal motoneurons are likely to reflect the combined influence of all the motor skills that share these motoneurons. KEY POINTS: Neuronal action potentials normally begin in the axon initial segment (AIS). AIS plasticity affects neuronal excitability in development and disease. Whether it does so in learning is unknown. Operant conditioning of a spinal reflex, a simple learning model, changes the rat spinal motoneuron AIS. Successful, but not unsuccessful, H-reflex up-conditioning is associated with greater AIS length and distance from soma. Successful, but not unsuccessful, down-conditioning is associated with more AIS GABAergic terminals, less ankyrin G, and more p-p38 protein kinase. The associations between AIS plasticity and successful H-reflex conditioning are consistent with those between AIS plasticity and functional changes in development and disease, and with those predicted by modelling studies in the literature. Motor learning changes neurons and synapses in spinal cord and brain. Because spinal motoneurons are the final common pathway for behaviour, their AIS properties probably reflect the combined impact of all the behaviours that use these motoneurons.</p>10aAnimals10aAnkyrins10aAxon Initial Segment10aAxons10aConditioning, Operant10aH-Reflex10aLearning10aMale10aMotor Neurons10aNeuronal Plasticity10aRats10aRats, Sprague-Dawley10aSpinal Cord1 aWang, Yu1 aChen, Yi1 aChen, Lu1 aHerron, Bruce, J1 aChen, Xiang, Yang1 aWolpaw, Jonathan, R  uhttps://www.neurotechcenter.org/publications/2024/motor-learning-changes-axon-initial-segment-spinal-motoneuron02675nas a2200325   4500008004100000022001400041245010000055210006900155260001200224300001200236490000800248520178700256653001202043653002602055653001102081653001302092653001302105653001502118653000902133653000902142653002502151653002502176100001302201700001302214700001902227700001302246700002102259700002102280856004802301       2014                        eng d  a1522-159800aLocomotor impact of beneficial or nonbeneficial H-reflex conditioning after spinal cord injury.0 aLocomotor impact of beneficial or nonbeneficial Hreflex conditio  c03/2014  a1249-580 v1113 aWhen new motor learning changes neurons and synapses in the spinal cord, it may affect previously learned behaviors that depend on the same spinal neurons and synapses. To explore these effects, we used operant conditioning to strengthen or weaken the right soleus H-reflex pathway in rats in which a right spinal cord contusion had impaired locomotion. When up-conditioning increased the H-reflex, locomotion improved. Steps became longer, and step-cycle asymmetry (i.e., limping) disappeared. In contrast, when down-conditioning decreased the H-reflex, locomotion did not worsen. Steps did not become shorter, and asymmetry did not increase. Electromyographic and kinematic analyses explained how H-reflex increase improved locomotion and why H-reflex decrease did not further impair it. Although the impact of up-conditioning or down-conditioning on the H-reflex pathway was still present during locomotion, only up-conditioning affected the soleus locomotor burst. Additionally, compensatory plasticity apparently prevented the weaker H-reflex pathway caused by down-conditioning from weakening the locomotor burst and further impairing locomotion. The results support the hypothesis that the state of the spinal cord is a "negotiated equilibrium" that serves all the behaviors that depend on it. When new learning changes the spinal cord, old behaviors undergo concurrent relearning that preserves or improves their key features. Thus, if an old behavior has been impaired by trauma or disease, spinal reflex conditioning, by changing a specific pathway and triggering a new negotiation, may enable recovery beyond that achieved simply by practicing the old behavior. Spinal reflex conditioning protocols might complement other neurorehabilitation methods and enhance recovery.10aAnimals10aConditioning, Operant10aFemale10aH-Reflex10aLearning10aLocomotion10aMale10aRats10aRats, Sprague-Dawley10aSpinal Cord Injuries1 aChen, Yi1 aChen, Lu1 aLiu, Rongliang1 aWang, Yu1 aChen, Xiang Yang1 aWolpaw, Jonathan  uhttp://www.ncbi.nlm.nih.gov/pubmed/2437128802425nas a2200289   4500008004100000022001400041245008700055210006900142260001200211300001200223490000800235520161100243653002601854653001301880653001501893653001101908653001801919653001901937653002301956653002701979100001302006700001302019700001302032700002102045700002102066856004802087       2014                        eng d  a1522-159800aPersistent beneficial impact of H-reflex conditioning in spinal cord-injured rats.0 aPersistent beneficial impact of Hreflex conditioning in spinal c  c11/2014  a2374-810 v1123 a<p>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.</p>10aH-reflex conditioning10aLearning10aLocomotion10aMemory10aMotor control10aRehabilitation10aspinal cord injury10aspinal cord plasticity1 aChen, Yi1 aChen, Lu1 aWang, Yu1 aWolpaw, Jonathan1 aChen, Xiang Yang  uhttp://www.ncbi.nlm.nih.gov/pubmed/2514354202704nas a2200241   4500008004100000022001400041245009000055210006900145260001200214300001400226490000700240520199800247653003402245653001302279653001102292653001802303653001602321100002202337700001302359700002102372700002102393856004802414       2008                        eng d  a1460-956800aEffects of H-reflex up-conditioning on GABAergic terminals on rat soleus motoneurons.0 aEffects of Hreflex upconditioning on GABAergic terminals on rat   c08/2008  a668–6740 v283 aTo 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.10aactivity-dependent plasticity10aLearning10aMemory10aMotor control10aSpinal Cord1 aPillai, Shreejith1 aWang, Yu1 aWolpaw, Jonathan1 aChen, Xiang Yang  uhttp://www.ncbi.nlm.nih.gov/pubmed/18657184