03907nas a2200361   4500008004100000022001400041245007800055210006900133260001300202300001400215490000800229520287700237653001203114653001303126653002503139653001003164653002603174653001303200653001303213653000903226653001803235653002403253653000903277653002503286653001603311100001303327700001303340700001303353700002103366700002203387700002403409856011203433       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://neurotechcenter.org/publications/2024/motor-learning-changes-axon-initial-segment-spinal-motoneuron00801nas a2200229   4500008004100000022001400041245013800055210006900193260001300262300000800275490000800283653002600291653001300317653001100330653002100341653001100362653001600373653002500389100002000414700002200434856011500456       2024                        eng d  a1872-895200aOperant up-conditioning of the soleus cutaneous reflex to non-noxious stimuli in a person with chronic incomplete spinal cord injury.0 aOperant upconditioning of the soleus cutaneous reflex to nonnoxi  c2024 Jan  a1-30 v15710aConditioning, Operant10aH-Reflex10aHumans10aMuscle, Skeletal10aReflex10aSpinal Cord10aSpinal Cord Injuries1 aPhipps, Alan, M1 aThompson, Aiko, K  uhttps://neurotechcenter.org/publications/2024/operant-conditioning-soleus-cutaneous-reflex-non-noxious-stimuli02131nas a2200253   4500008004100000245007200041210006900113260000900182300001400191490000700205520141800212653001301630653001901643653002501662653001501687653001901702653001601721100001301737700001301750700001301763700002201776700002101798856005801819       2017                        eng d00aWhy New Spinal Cord Plasticity Does Not Disrupt Old Motor Behaviors0 aWhy New Spinal Cord Plasticity Does Not Disrupt Old Motor Behavi  cJuly  a8198-82060 v373 aWhen new motor learning changes the spinal cord, old behaviors are not impaired; their key features are preserved by additional compensatory plasticity. To explore the mechanisms responsible for this compensatory plasticity, we transected the spinal dorsal ascending tract before or after female rats acquired a new behavior—operantly conditioned increase or decrease in the right soleus H-reflex—and examined an old behavior—locomotion. Neither spinal dorsal ascending tract transection nor H-reflex conditioning alone impaired locomotion. Nevertheless, when spinal dorsal ascending tract transection and H-reflex conditioning were combined, the rats developed a limp and a tilted posture that correlated in direction and magnitude with the H-reflex change. When the right H-reflex was increased by conditioning, the right step lasted longer than the left and the right hip was higher than the left; when the right H-reflex was decreased by conditioning, the opposite occurred. These results indicate that ascending sensory input guides the compensatory plasticity that normally prevents the plasticity underlying H-reflex change from impairing locomotion. They support the concept of the state of the spinal cord as a negotiated equilibrium that reflects the concurrent influences of all the behaviors in an individual's repertoire; and they support the new therapeutic strategies this concept introduces.10aH-Reflex10amotor learning10aoperant conditioning10aplasticity10aRehabilitation10aSpinal Cord1 aChen, Yi1 aChen, Lu1 aWang, Yu1 aChen, Xiang, Yang1 aWolpaw, Jonathan  uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5566867/01650nas a2200205   4500008004100000022001400041245008000055210006900135260000800204300001600212490000800228520106300236653001601299100002101315700001301336700001301349700001301362700002101375856004801396       2016                        eng d  a1522-159800aAblation of the inferior olive prevents H-reflex down-conditioning in rats.0 aAblation of the inferior olive prevents Hreflex downconditioning  cMar  a1630–16360 v1153 aWe evaluated the role of the inferior olive (IO) in acquisition of the spinal cord plasticity that underlies H-reflex down-conditioning, a simple motor skill. The IO was chemically ablated before a 50-day exposure to an operant conditioning protocol that rewarded a smaller soleus H-reflex. In normal rats, down-conditioning succeeds (i.e., H-reflex size decreases at least 20%) in 80% of animals. Down-conditioning failed in every IO-ablated rat (P< 0.001 vs. normal rats). IO ablation itself had no long-term effect on H-reflex size. These results indicate that the IO is essential for acquisition of a down-conditioned H-reflex. With previous data, they support the hypothesis that IO and cortical inputs to cerebellum enable the cerebellum to guide sensorimotor cortex plasticity that produces and maintains the spinal cord plasticity that underlies the down-conditioned H-reflex. They help to further define H-reflex conditioning as a model for understanding motor learning and as a new approach to enhancing functional recovery after trauma or disease.10aSpinal Cord1 aChen, Xiang Yang1 aWang, Yu1 aChen, Yi1 aChen, Lu1 aWolpaw, Jonathan  uhttp://www.ncbi.nlm.nih.gov/pubmed/2679288802314nas a2200229   4500008004100000022001400041245010300055210006900158260001200227300001200239490000800251520162300259653002901882653001101911653001301922653001801935653001601953100002501969700002101994700002102015856004802036       2015                        eng d  a1522-159800aElectrocorticographic activity over sensorimotor cortex and motor function in awake behaving rats.0 aElectrocorticographic activity over sensorimotor cortex and moto  c04/2015  a2232-410 v1133 a<p>Sensorimotor cortex exerts both short-term and long-term control over the spinal reflex pathways that serve motor behaviors. Better understanding of this control could offer new possibilities for restoring function after central nervous system trauma or disease. We examined the impact of ongoing sensorimotor cortex (SMC) activity on the largely monosynaptic pathway of the H-reflex, the electrical analog of the spinal stretch reflex. In 41 awake adult rats, we measured soleus electromyographic (EMG) activity, the soleus H-reflex, and electrocorticographic activity over the contralateral SMC while rats were producing steady-state soleus EMG activity. Principal component analysis of electrocorticographic frequency spectra before H-reflex elicitation consistently revealed three frequency bands: μβ (5-30 Hz), low γ (γ1; 40-85 Hz), and high γ (γ2; 100-200 Hz). Ongoing (i.e., background) soleus EMG amplitude correlated negatively with μβ power and positively with γ1 power. In contrast, H-reflex size correlated positively with μβ power and negatively with γ1 power, but only when background soleus EMG amplitude was included in the linear model. These results support the hypothesis that increased SMC activation (indicated by decrease in μβ power and/or increase in γ1 power) simultaneously potentiates the H-reflex by exciting spinal motoneurons and suppresses it by decreasing the efficacy of the afferent input. They may help guide the development of new rehabilitation methods and of brain-computer interfaces that use SMC activity as a substitute for lost or impaired motor outputs.</p>10abrain-computer interface10acortex10aH-Reflex10aMotor control10aSpinal Cord1 aBoulay, Chadwick, B.1 aChen, Xiang Yang1 aWolpaw, Jonathan  uhttp://www.ncbi.nlm.nih.gov/pubmed/2563207602554nas a2200241   4500008004100000022001400041245016400055210006900219260001200288300001200300490000800312520178000320653001302100653001502113653001902128653001602147653001502163100002102178700002202199700002102221700002202242856004802264       2014                        eng d  a1522-159800aOperant conditioning of the soleus H-reflex does not induce long-term changes in the gastrocnemius H-reflexes and does not disturb normal locomotion in humans.0 aOperant conditioning of the soleus Hreflex does not induce longt  c09/2014  a1439-460 v1123 a<p>In normal animals, operant conditioning of the spinal stretch reflex or the H-reflex has lesser effects on synergist muscle reflexes. In rats and people with incomplete spinal cord injury (SCI), soleus H-reflex operant conditioning can improve locomotion. We studied in normal humans the impact of soleus H-reflex down-conditioning on medial (MG) and lateral gastrocnemius (LG) H-reflexes and on locomotion. Subjects completed 6 baseline and 30 conditioning sessions. During conditioning trials, the subject was encouraged to decrease soleus H-reflex size with the aid of visual feedback. Every sixth session, MG and LG H-reflexes were measured. Locomotion was assessed before and after conditioning. In successfully conditioned subjects, the soleus H-reflex decreased 27.2%. This was the sum of within-session (task dependent) adaptation (13.2%) and across-session (long term) change (14%). The MG H-reflex decreased 14.5%, due mainly to task-dependent adaptation (13.4%). The LG H-reflex showed no task-dependent adaptation or long-term change. No consistent changes were detected across subjects in locomotor H-reflexes, EMG activity, joint angles, or step symmetry. Thus, in normal humans, soleus H-reflex down-conditioning does not induce long-term changes in MG/LG H-reflexes and does not change locomotion. In these subjects, task-dependent adaptation of the soleus H-reflex is greater than it is in people with SCI, whereas long-term change is less. This difference from results in people with SCI is consistent with the fact that long-term change is beneficial in people with SCI, since it improves locomotion. In contrast, in normal subjects, long-term change is not beneficial and may necessitate compensatory plasticity to preserve satisfactory locomotion.</p>10aLearning10aplasticity10aRehabilitation10aSpinal Cord10asynergists1 aMakihara, Yukiko1 aSegal, Richard, L1 aWolpaw, Jonathan1 aThompson, Aiko, K  uhttp://www.ncbi.nlm.nih.gov/pubmed/2494421601203nas a2200277   4500008004100000022001400041245009000055210006900145260001200214300001000226490000700236520041500243653001200658653002600670653001300696653001100709653001700720653002100737653002400758653001100782653001600793653002500809100002200834700002100856856004800877       2014                        eng d  a1538-300800aThe simplest motor skill: mechanisms and applications of reflex operant conditioning.0 asimplest motor skill mechanisms and applications of reflex opera  c04/2014  a82-900 v423 aOperant conditioning protocols can change spinal reflexes gradually, which are the simplest behaviors. This article summarizes the evidence supporting two propositions: that these protocols provide excellent models for defining the substrates of learning and that they can induce and guide plasticity to help restore skills, such as locomotion, that have been impaired by spinal cord injury or other disorders.10aAnimals10aConditioning, Operant10aH-Reflex10aHumans10aMotor Skills10aMuscle, Skeletal10aNeuronal Plasticity10aReflex10aSpinal Cord10aSpinal Cord Injuries1 aThompson, Aiko, K1 aWolpaw, Jonathan  uhttp://www.ncbi.nlm.nih.gov/pubmed/2450873801657nas a2200217   4500008004100000022001400041245008100055210006900136260001200205300001400217490000700231520101900238653001901257653001501276653001901291653001601310100002301326700002101349700002101370856004801391       2013                        eng d  a1097-459800aSoleus H-reflex operant conditioning changes the H-reflex recruitment curve.0 aSoleus Hreflex operant conditioning changes the Hreflex recruitm  c04/2013  a539–5440 v473 aINTRODUCTION:
Operant conditioning can gradually change the human soleus H-reflex. The protocol conditions the reflex near M-wave threshold. In this study we examine its impact on the reflexes at other stimulus strengths.
METHODS:
H-reflex recruitment curves were obtained before and after a 24-session exposure to an up-conditioning (HRup) or a down-conditioning (HRdown) protocol and were compared.
RESULTS:
In both HRup and HRdown subjects, conditioning affected the entire H-reflex recruitment curve. In 5 of 6 HRup and 3 of 6 HRdown subjects, conditioning elevated (HRup) or depressed (HRdown), respectively, the entire curve. In the other HRup subject or the other 3 HRdown subjects, the curve was shifted to the left or to the right, respectively.
CONCLUSIONS:
H-reflex conditioning does not simply change the H-reflex to a stimulus of particular strength; it also changes the H-reflexes to stimuli of different strengths. Thus, it is likely to affect many actions in which this pathway participates.10amotor learning10aplasticity10aRehabilitation10aSpinal Cord1 aThompson, Aiko, K.1 aChen, Xiang Yang1 aWolpaw, Jonathan  uhttp://www.ncbi.nlm.nih.gov/pubmed/2328110701486nas a2200205   4500008004100000022001400041245010200055210006900157260001200226300001600238490000800254520087300262653001601135100001301151700001301164700001301177700002101190700002101211856004801232       2012                        eng d  a1522-159800aCortical stimulation causes long-term changes in H-reflexes and spinal motoneuron GABA receptors.0 aCortical stimulation causes longterm changes in Hreflexes and sp  c11/2012  a2668–26780 v1083 aThe cortex gradually modifies the spinal cord during development, throughout later life, and in response to trauma or disease. The mechanisms of this essential function are not well understood. In this study, weak electrical stimulation of rat sensorimotor cortex increased the soleus H-reflex, increased the numbers and sizes of GABAergic spinal interneurons and GABAergic terminals on soleus motoneurons, and decreased GABA(A) and GABA(B) receptor labeling in these motoneurons. Several months after the stimulation ended the interneuron and terminal increases had disappeared, but the H-reflex increase and the receptor decreases remained. The changes in GABAergic terminals and GABA(B) receptors accurately predicted the changes in H-reflex size. The results reveal a new long-term dimension to cortical-spinal interactions and raise new therapeutic possibilities.10aSpinal Cord1 aWang, Yu1 aChen, Yi1 aChen, Lu1 aWolpaw, Jonathan1 aChen, Xiang Yang  uhttp://www.ncbi.nlm.nih.gov/pubmed/2293371802599nas a2200289   4500008004100000022001400041245013200055210006900187260001200256300001800268490000700286520174900293653001702042653002102059653001502080653001102095653001702106653001602123100001302139700001302152700001302165700001702178700002402195700002102219700002102240856004802261       2010                        eng d  a1529-240100aH-reflex up-conditioning encourages recovery of EMG activity and H-reflexes after sciatic nerve transection and repair in rats.0 aHreflex upconditioning encourages recovery of EMG activity and H  c12/2010  a16128–161360 v303 aOperant conditioning of the spinal stretch reflex or its electrical analog, the H-reflex, produces spinal cord plasticity and can thereby affect motoneuron responses to primary afferent input. To explore whether this conditioning can affect the functional outcome after peripheral nerve injury, we assessed the effect of up-conditioning soleus (SOL) H-reflex on SOL and tibialis anterior (TA) function after sciatic nerve transection and repair. Sprague Dawley rats were implanted with EMG electrodes in SOL and TA and stimulating cuffs on the posterior tibial nerve. After control data collection, the sciatic nerve was transected and repaired and the rat was exposed for 120 d to continued control data collection (TC rats) or SOL H-reflex up-conditioning (TU rats). At the end of data collection, motoneurons that had reinnervated SOL and TA were labeled retrogradely. Putative primary afferent terminals [i.e., terminals containing vesicular glutamate transporter-1 (VGLUT1)] on SOL motoneurons were studied immunohistochemically. SOL (and probably TA) background EMG activity recovered faster in TU rats than in TC rats, and the final recovered SOL H-reflex was significantly larger in TU than in TC rats. TU and TC rats had significantly fewer labeled motoneurons and higher proportions of double-labeled motoneurons than untransected rats. VGLUT1 terminals were significantly more numerous on SOL motoneurons of TU than TC rats. Combined with the larger H-reflexes in TU rats, this anatomical finding supports the hypothesis that SOL H-reflex up-conditioning strengthened primary afferent reinnervation of SOL motoneurons. These results suggest that H-reflex up-conditioning may improve functional recovery after nerve injury and repair.10aconditioning10aperipheral nerve10aplasticity10aReflex10aregeneration10aSpinal Cord1 aChen, Yi1 aWang, Yu1 aChen, Lu1 aSun, Chenyou1 aEnglish, Arthur, W.1 aWolpaw, Jonathan1 aChen, Xiang Yang  uhttp://www.ncbi.nlm.nih.gov/pubmed/2112355901829nas a2200157   4500008004100000022001400041245006600055210006400121260001200185300001400197490000700211520136800218653001601586100002101602856004801623       2010                        eng d  a1089-409800aWhat can the spinal cord teach us about learning and memory?.0 aWhat can the spinal cord teach us about learning and memory  c10/2010  a532–5490 v163 aThe work of recent decades has shown that the nervous system changes continually throughout life. Activity-dependent central nervous system (CNS) plasticity has many different mechanisms and involves essentially every region, from the cortex to the spinal cord. This new knowledge radically changes the challenge of explaining learning and memory and greatly increases the relevance of the spinal cord. The challenge is now to explain how continual and ubiquitous plasticity accounts for the initial acquisition and subsequent stability of many different learned behaviors. The spinal cord has a key role because it is the final common pathway for all behavior and is a site of substantial plasticity. Furthermore, because it is simple, accessible, distant from the rest of the CNS, and directly connected to behavior, the spinal cord is uniquely suited for identifying sites and mechanisms of plasticity and for determining how they account for behavioral change. Experimental models based on spinal cord reflexes facilitate study of the gradual plasticity that makes possible most rapid learning phenomena. These models reveal principles and generate concepts that are likely to apply to learning and memory throughout the CNS. In addition, they offer new approaches to guiding activity-dependent plasticity so as to restore functions lost to injury or disease.10aSpinal Cord1 aWolpaw, Jonathan  uhttp://www.ncbi.nlm.nih.gov/pubmed/2088996402476nas a2200241   4500008004100000022001400041245011900055210006900174260001200243300001600255490000700271520173900278653001302017653001902030653001602049653002502065653001502090653001602105100002302121700002102144700002102165856004802186       2009                        eng d  a1529-240100aAcquisition of a simple motor skill: task-dependent adaptation plus long-term change in the human soleus H-reflex.0 aAcquisition of a simple motor skill taskdependent adaptation plu  c05/2009  a5784–57920 v293 aActivity-dependent plasticity occurs throughout the CNS. However, investigations of skill acquisition usually focus on cortex. To expand the focus, we analyzed in humans the development of operantly conditioned H-reflex change, a simple motor skill that develops gradually and involves plasticity in both the brain and the spinal cord. Each person completed 6 baseline and 24 conditioning sessions over 10 weeks. In each conditioning session, the soleus H-reflex was measured while the subject was or was not asked to increase (HRup subjects) or decrease (HRdown subjects) it. When the subject was asked to change H-reflex size, immediate visual feedback indicated whether a size criterion had been satisfied. Over the 24 conditioning sessions, H-reflex size gradually increased in six of eight HRup subjects and decreased in eight of nine HRdown subjects, resulting in final sizes of 140 +/- 12 and 69 +/- 6% of baseline size, respectively. The final H-reflex change was the sum of within-session (i.e., task-dependent) adaptation and across-session (i.e., long-term) change. Task-dependent adaptation appeared within four to six sessions and persisted thereafter, averaging +13% in HRup subjects and -15% in HRdown subjects. In contrast, long-term change began after 10 sessions and increased gradually thereafter, reaching +27% in HRup subjects and -16% in HRdown subjects. Thus, the acquisition of H-reflex conditioning consists of two phenomena, task-dependent adaptation and long-term change, that together constitute the new motor skill. In combination with previous data, this new finding further elucidates the interaction of plasticity in brain and spinal cord that underlies the acquisition and maintenance of motor skills.10aH-Reflex10amotor learning10amotor skill10aoperant conditioning10aplasticity10aSpinal Cord1 aThompson, Aiko, K.1 aChen, Xiang Yang1 aWolpaw, Jonathan  uhttp://www.ncbi.nlm.nih.gov/pubmed/1942024601505nas a2200253   4500008004100000022001400041245012000055210006900175260001200244300001400256490000800270520070300278653003400981653002701015653002601042653002401068653001801092653001601110100001301126700002201139700002101161700002101182856004801203       2009                        eng d  a0304-394000aH-reflex down-conditioning greatly increases the number of identifiable GABAergic interneurons in rat ventral horn.0 aHreflex downconditioning greatly increases the number of identif  c03/2009  a124–1290 v4523 aH-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.10aactivity-dependent plasticity10aGABAergic interneurons10aH-reflex conditioning10alearning and memory10aMotor control10aSpinal Cord1 aWang, Yu1 aPillai, Shreejith1 aWolpaw, Jonathan1 aChen, Xiang Yang  uhttp://www.ncbi.nlm.nih.gov/pubmed/1938342602704nas 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/1865718402251nas a2200169   4500008004100000022001400041245013300055210006900188260001200257300001400269490000700283520168500290653001601975100002101991700002102012856004802033       2006                        eng d  a1072-050200aThe cerebellum in maintenance of a motor skill: a hierarchy of brain and spinal cord plasticity underlies H-reflex conditioning.0 acerebellum in maintenance of a motor skill a hierarchy of brain   c03/2006  a208–2150 v133 aOperant conditioning of the H-reflex, the electrical analog of the spinal stretch reflex, is a simple model of skill acquisition and involves plasticity in the spinal cord. Previous work showed that the cerebellum is essential for down-conditioning the H-reflex. This study asks whether the cerebellum is also essential for maintaining down-conditioning. After rats decreased the soleus H-reflex over 50 d in response to the down-conditioning protocol, the cerebellar output nuclei dentate and interpositus (DIN) were ablated, and down-conditioning continued for 50-100 more days. In naive (i.e., unconditioned) rats, DIN ablation itself has no significant long-term effect on H-reflex size. During down-conditioning prior to DIN ablation, eight Sprague-Dawley rats decreased the H-reflex to 57% (+/-4 SEM) of control. It rose after ablation, stabilizing within 2 d at about 75% and remaining there until approximately 40 d after ablation. It then rose to approximately 130%, where it remained through the end of study 100 d after ablation. Thus, DIN ablation in down-conditioned rats caused an immediate increase and a delayed increase in the H-reflex. The final result was an H-reflex significantly larger than that prior to down-conditioning. Combined with previous work, these remarkable results suggest that the spinal cord plasticity directly responsible for down-conditioning, which survives only 5-10 d on its own, is maintained by supraspinal plasticity that survives approximately 40 d after loss of cerebellar output. Thus, H-reflex conditioning seems to depend on a hierarchy of brain and spinal cord plasticity to which the cerebellum makes an essential contribution.10aSpinal Cord1 aWolpaw, Jonathan1 aChen, Xiang Yang  uhttp://www.ncbi.nlm.nih.gov/pubmed/1658579602091nas a2200253   4500008004100000022001400041245004000055210003800095260001200133300001400145490000800159520142300167653002101590653002101611653002501632653001701657653001101674653001601685100002301701700002301724700002101747700002101768856004801789       2006                        eng d  a0014-481900aDiurnal H-reflex variation in mice.0 aDiurnal Hreflex variation in mice  c01/2006  a517–5280 v1683 aMice exhibit diurnal variation in complex motor behaviors, but little is known about diurnal variation in simple spinally mediated functions. This study describes diurnal variation in the H-reflex (HR), a wholly spinal and largely monosynaptic reflex. Six mice were implanted with tibial nerve cuff electrodes and electrodes in the soleus and gastrocnemius muscles, for recording of ongoing and nerve-evoked electromyographic activity (EMG). Stimulation and recording were under computer control 24 h/day. During a 10-day recording period, HR amplitude varied throughout the day, usually being larger in the dark than in the light. This diurnal HR variation could not be attributed solely to differences in the net ongoing level of descending and segmental excitation to the spinal cord or stimulus intensity. HRs were larger in the dark than in the light even after restricting the evoked responses to subsets of trials having similar ongoing EMG and M-responses. The diurnal variation in the HR was out of phase with that reported previously for rats, but was in phase with that observed in monkeys. These data, supported by those in other species, suggest that the supraspinal control of the excitability of the HR pathway varies throughout the day in a species-specific pattern. This variation should be taken into account in experimental and clinical studies of spinal reflexes recorded at different times of day.10acircadian rhythm10aElectromyography10aimplanted electrodes10aMonosynaptic10aReflex10aSpinal Cord1 aCarp, Jonathan, S.1 aTennissen, Ann, M.1 aChen, Xiang Yang1 aWolpaw, Jonathan  uhttp://www.ncbi.nlm.nih.gov/pubmed/1615178101977nas a2200229   4500008004100000022001400041245005500055210004900110260001200159300001400171490000800185520137700193653001301570653001701583653001301600653001101613653001501624653001601639653002301655100002101678856004801699       2006                        eng d  a0079-612300aThe education and re-education of the spinal cord.0 aeducation and reeducation of the spinal cord  c02/2006  a261–2800 v1573 aIn normal life, activity-dependent plasticity occurs in the spinal cord as well as in the brain. Like CNS plasticity elsewhere, this spinal cord plasticity can occur at many neuronal and synaptic sites and by a variety of mechanisms. Spinal cord plasticity is prominent in postnatal development and contributes to acquisition of standard behaviors such as locomotion and rapid withdrawal from pain. Later on in life, spinal cord plasticity contributes to acquisition and maintenance of specialized motor skills, and to compensation for the peripheral and central changes associated with aging, disease, and trauma. Mastery of even the simplest behaviors is accompanied by complex spinal and supraspinal plasticity. This complexity is necessary, to preserve the full roster of behaviors, and is also inevitable, due to the ubiquity of activity-dependent plasticity in the CNS. Careful investigation of spinal cord plasticity is essential for understanding motor skills; and, because of the relative simplicity and accessibility of the spinal cord, is a logical and convenient starting point for exploring skill acquisition. Appropriate induction and guidance of activity-dependent plasticity in the spinal cord is likely to be a key part of the realization of effective new rehabilitation methods for spinal cord injuries, cerebral palsy, and other chronic motor disorders.10abehavior10aconditioning10aLearning10aMemory10aplasticity10aSpinal Cord10aspinal cord injury1 aWolpaw, Jonathan  uhttp://www.ncbi.nlm.nih.gov/pubmed/1716791602319nas a2200193   4500008004100000022001400041245004300055210004100098260001200139300001600151490000700167520179900174653001601973100002301989700002302012700002102035700002102056856004802077       2006                        eng d  a0022-307700aH-reflex operant conditioning in mice.0 aHreflex operant conditioning in mice  c10/2006  a1718–17270 v963 aRats, monkeys, and humans can alter the size of their spinal stretch reflex and its electrically induced analog, the H-reflex (HR), when exposed to an operant conditioning paradigm. Because this conditioning induces plasticity in the spinal cord, it offers a unique opportunity to identify the neuronal sites and mechanisms that underlie a well-defined change in a simple behavior. To facilitate these studies, we developed an HR operant conditioning protocol in mice, which are better suited to genetic manipulation and electrophysiological spinal cord study in vitro than rats or primates. Eleven mice under deep surgical anesthesia were implanted with tibial nerve stimulating electrodes and soleus and gastrocnemius intramuscular electrodes for recording ongoing and stimulus-evoked EMG activity. During the 24-h/day computer-controlled experiment, mice received a liquid reward for either increasing (up-conditioning) or decreasing (down-conditioning) HR amplitude while maintaining target levels of ongoing EMG and directly evoked EMG (M-responses). After 3-7 wk of conditioning, the HR amplitude was 133 +/- 7% (SE) of control for up-conditioning and 71 +/- 8% of control for down-conditioning. HR conditioning was successful (i.e., > or =20% change in HR amplitude in the appropriate direction) in five of six up-conditioned animals (mean final HR amplitude = 139 +/- 5% of control HR for successful mice) and in four of five down-conditioned animals (mean final HR amplitude = 63 +/- 8% of control HR for successful mice). These effects were not attributable to differences in the net level of motoneuron pool excitation, stimulation strength, or distribution of HR trials throughout the day. Thus mice exhibit HR operant conditioning comparable with that observed in rats and monkeys.10aSpinal Cord1 aCarp, Jonathan, S.1 aTennissen, Ann, M.1 aChen, Xiang Yang1 aWolpaw, Jonathan  uhttp://www.ncbi.nlm.nih.gov/pubmed/1683765902744nas a2200193   4500008004100000022001400041245011800055210006900173260001200242300001600254490000600270520212200276653001602398100002302414700002302437700002102460700002102481856004802502       2006                        eng d  a1557-170X00aModulation in spinal circuits and corticospinal connections following nerve stimulation and operant conditioning.0 aModulation in spinal circuits and corticospinal connections foll  c09/2006  a2138–21410 v13 aNeural plasticity occurs throughout adult life. In healthy individuals, different spinal pathways are differently modulated during different daily activities. Drastic changes to nervous system activity and connections caused by injuries or diseases alter spinal reflexes, and this is often related to disturbed motor functions. In both health and disease, spinal reflexes are subject to substantial modifications. Plasticity in supraspinal descending connections is even more remarkable; corticospinal connectivity has been shown to be extremely plastic. In this session, we describe two approaches for possibly improving recovery after central nervous system (CNS) lesions. They are very different, but both involve repetitive nerve stimulation and CNS plasticity. The first approach is functional electrical stimulation (FES) of the common peroneal nerve, which has been used to treat foot drop in patients with CNS lesions. The second approach is operant conditioning of a spinal reflex. Spinal reflex operant conditioning studies in animal models have shown plastic changes in spinal cord neurons associated with this form of learning and improved locomotor function in incomplete spinal cord injured rats. Thus, reflex conditioning might be a robust approach to inducing plasticity at spinal and supraspinal levels. As a first step in establishing this approach and characterizing its effects in the human adult CNS, we are currently investigating the extent and time course of operant conditioning of the soleus H-reflex in healthy subjects. In results to date, all subjects (n=5) have changed reflex size in the correct direction to various degree (16-36%) over 2-3 months of conditioning, indicating possibility that H-reflex conditioning can occur in humans. At the same time, the substantial inter-subject variation in the time course and extent of conditioning suggest that additional data are needed to establish its principal features. We hope that studying modulation and modification o- f the CNS by different approaches will help us further understand the plasticity of the human adult nervous system.10aSpinal Cord1 aThompson, Aiko, K.1 aStein, Richard, B.1 aChen, Xiang Yang1 aWolpaw, Jonathan  uhttp://www.ncbi.nlm.nih.gov/pubmed/1794693902175nas a2200253   4500008004100000022001400041245008500055210006900140260001200209300001400221490000700235520145300242653003401695653000901729653001301738653001101751653001801762653001601780100001301796700002201809700002101831700002101852856004801873       2006                        eng d  a0953-816X00aMotor learning changes GABAergic terminals on spinal motoneurons in normal rats.0 aMotor learning changes GABAergic terminals on spinal motoneurons  c01/2006  a141–1500 v233 aThe 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.10aactivity-dependent plasticity10aGABA10aH-Reflex10aMemory10aMotor control10aSpinal Cord1 aWang, Yu1 aPillai, Shreejith1 aWolpaw, Jonathan1 aChen, Xiang Yang  uhttp://www.ncbi.nlm.nih.gov/pubmed/1642042402190nas a2200253   4500008004100000022001400041245009500055210006900150260001200219300001600231490000800247520145200255653001301707653001501720653001101735653001501746653001601761100002501777700001901802700002201821700002101843700002401864856004801888       2006                        eng d  a1388-245700aPlastic changes in the human H-reflex pathway at rest following skillful cycling training.0 aPlastic changes in the human Hreflex pathway at rest following s  c08/2006  a1682–16910 v1173 aOBJECTIVE:
The spinal cord is capable of activity-dependent plasticity, but the extent of its participation in human motor learning is not known. Here, we tested the hypothesis that acquisition of a locomotor-related skill modulates the pathway of the H-reflex, a measure of spinal cord excitability that is susceptible to plastic changes.
METHODS:
Subjects were tested on their ability to establish a constant cycling speed on a recumbent bike despite frequent changes in pedal resistance. The coefficient of variation of speed (CV(speed)) measured their ability to acquire this skill (decreasing CV(speed) with training reflects performance improvements). Soleus H-reflexes were taken at rest before and after cycling.
RESULTS:
Ability to establish a target speed increased and H-reflex size decreased more after cycling training involving frequent changes in pedal resistance that required calibrated locomotor compensatory action than with training involving constant pedal resistances and lesser compensation. The degree of performance improvement correlated with the reduction in the amplitude of the H-reflex.
CONCLUSIONS:
Skillful establishment of a constant cycling speed despite changing pedal resistances is associated with persistent modulation of activity in spinal pathways.
SIGNIFICANCE:
Recalibration of activity in the H-reflex pathway may be part of the control strategy required for locomotor-related skill acquisition.10aH-Reflex10aLocomotion10aMemory10aplasticity10aSpinal Cord1 aMazzocchio, Riccardo1 aKitago, Tomoko1 aLiuzzi, Gianpiero1 aWolpaw, Jonathan1 aCohen, Leonardo, G.  uhttp://www.ncbi.nlm.nih.gov/pubmed/1679333302728nas a2200253   4500008004100000022001400041245003700055210003600092260001200128300001400140490000700154520210100161653002302262653001602285653001302301653001102314653001502325653001102340653001502351653001602366100002102382700002302403856004802426       2006                        eng d  a0301-008200aPlasticity from muscle to brain.0 aPlasticity from muscle to brain  c02/2006  a233–2630 v783 aRecognition that the entire central nervous system (CNS) is highly plastic, and that it changes continually throughout life, is a relatively new development. Until very recently, neuroscience has been dominated by the belief that the nervous system is hardwired and changes at only a few selected sites and by only a few mechanisms. Thus, it is particularly remarkable that Sir John Eccles, almost from the start of his long career nearly 80 years ago, focused repeatedly and productively on plasticity of many different kinds and in many different locations. He began with muscles, exploring their developmental plasticity and the functional effects of the level of motor unit activity and of cross-reinnervation. He moved into the spinal cord to study the effects of axotomy on motoneuron properties and the immediate and persistent functional effects of repetitive afferent stimulation. In work that combined these two areas, Eccles explored the influences of motoneurons and their muscle fibers on one another. He studied extensively simple spinal reflexes, especially stretch reflexes, exploring plasticity in these reflex pathways during development and in response to experimental manipulations of activity and innervation. In subsequent decades, Eccles focused on plasticity at central synapses in hippocampus, cerebellum, and neocortex. His endeavors extended from the plasticity associated with CNS lesions to the mechanisms responsible for the most complex and as yet mysterious products of neuronal plasticity, the substrates underlying learning and memory. At multiple levels, Eccles' work anticipated and helped shape present-day hypotheses and experiments. He provided novel observations that introduced new problems, and he produced insights that continue to be the foundation of ongoing basic and clinical research. This article reviews Eccles' experimental and theoretical contributions and their relationships to current endeavors and concepts. It emphasizes aspects of his contributions that are less well known at present and yet are directly relevant to contemporary issues.10aactivity-dependent10aJohn Eccles10aLearning10aMemory10amotor unit10amuscle10aplasticity10aSpinal Cord1 aWolpaw, Jonathan1 aCarp, Jonathan, S.  uhttp://www.ncbi.nlm.nih.gov/pubmed/1664718102315nas a2200241   4500008004100000022001400041245006000055210005800115260001200173300001400185490000800199520163200207653002101839653002501860653001701885653001601902100002301918700002301941700002101964700001901985700002102004856004802025       2005                        eng d  a0165-027000aLong-term spinal reflex studies in awake behaving mice.0 aLongterm spinal reflex studies in awake behaving mice  c12/2005  a134–1430 v1493 aThe increasing availability of genetic variants of mice has facilitated studies of the roles of specific molecules in specific behaviors. The contributions of such studies could be strengthened and extended by correlation with detailed information on the patterns of motor commands throughout the course of specific behaviors in freely moving animals. Previously reported methodologies for long-term recording of electromyographic activity (EMG) in mice using implanted electrodes were designed for intermittent, but not continuous operation. This report describes the fabrication, implantation, and utilization of fine wire electrodes for continuous long-term recordings of spontaneous and nerve-evoked EMG in mice. Six mice were implanted with a tibial nerve cuff electrode and EMG electrodes in soleus and gastrocnemius muscles. Wires exited through a skin button and traveled through an armored cable to an electrical commutator. In mice implanted for 59-144 days, ongoing EMG was monitored continuously (i.e., 24 h/day, 7 days/week) by computer for 18-92 days (total intermittent recording for 25-130 days). When the ongoing EMG criteria were met, the computer applied the nerve stimulus, recorded the evoked EMG response, and determined the size of the M-response (MR) and the H-reflex (HR). It continually adjusted stimulation intensity to maintain a stable MR size. Stable recordings of ongoing EMG, MR, and HR were obtained typically 3 weeks after implantation. This study demonstrates the feasibility of long-term continuous EMG recordings in mice for addressing a variety of neurophysiological and behavioral issues.10aElectromyography10aimplanted electrodes10aMonosynaptic10aSpinal Cord1 aCarp, Jonathan, S.1 aTennissen, Ann, M.1 aChen, Xiang Yang1 aSchalk, Gerwin1 aWolpaw, Jonathan  uhttp://www.ncbi.nlm.nih.gov/pubmed/1602684802242nas a2200241   4500008004100000022001400041245008800055210006900143260001200212300001400224490000800238520154300246653002401789653001301813653001501826653001501841653001601856100002301872700002101895700001501916700002101931856004801952       2001                        eng d  a0014-481900aOperant conditioning of rat H-reflex affects motoneuron axonal conduction velocity.0 aOperant conditioning of rat Hreflex affects motoneuron axonal co  c01/2001  a269–2730 v1363 aThis study assessed the effects of operant conditioning of the H-reflex on motoneuron axonal conduction velocity in the rat. After measurement of the control H-reflex size, rats were either exposed for at least 40 days to the HRup or HRdown conditioning mode, in which reward occurred only if the soleus H-reflex was greater than (HRup mode) or less than (HRdown mode) a criterion or continued under the control condition (HRcon mode) in which the H-reflex was simply measured. We then measured axonal conduction velocity of triceps surae motor units of HRup, HRdown, and HRcon rats by stimulating the axon in the ventral root and recording from the tibial nerve. Conduction velocity was 8% less in successful HRdown rats than in HRcon rats (P=0.02). Conduction velocity in HRup rats and unsuccessful HRdown rats was not significantly different from that in HRcon rats. Since recording bypassed the intra-spinal portion of the motoneuron, the change was clearly in the axon. This decrease was similar to the 6% decrease previously found in successful HRdown monkeys. Unsuccessful HRdown rats and monkeys did not show this decrease. This result suggests that the mechanism of HRdown conditioning is similar in rats and monkeys and provides further support for the hypothesis that HRdown conditioning decreases motoneuron excitability by producing a positive shift in firing threshold. While traditional theories of learning emphasize synaptic plasticity, neuronal plasticity may also contribute to operantly conditioned behavioral changes.10aconduction velocity10aH-Reflex10amotoneuron10aplasticity10aSpinal Cord1 aCarp, Jonathan, S.1 aChen, Xiang Yang1 aSheikh, H.1 aWolpaw, Jonathan  uhttp://www.ncbi.nlm.nih.gov/pubmed/1120629002143nas a2200217   4500008004100000022001400041245008000055210006900135260001200204300001400216490000800230520152500238653001701763653001301780653001101793653001501804653001601819100002101835700002101856856004801877       2001                        eng d  a0014-481900aOperant conditioning of rat H-reflex: effects on mean latency and duration.0 aOperant conditioning of rat Hreflex effects on mean latency and   c01/2001  a274–2790 v1363 aWe are currently studying the mechanisms of operantly conditioned changes in the H-reflex in the rat. Primate data suggest that H-reflex decrease is due to a positive shift in motoneuron firing threshold and a small decrease in the monosynaptic excitatory postsynaptic potential (EPSP), and that increase might be due to change in group-I oligosynaptic (especially disynaptic) input. To further evaluate the possibility of conditioned change in oligosynaptic input, we compared the mean latency (i.e., the average latency of the entire H-reflex) and the duration of control (i.e., pre-conditioning) H-reflexes with those of H-reflexes after up-conditioning or down-conditioning. Up-conditioning was associated with small, statistically significant increases in H-reflex mean latency [+0.11+/-0.05 (+/-SE) ms] and duration (+0.32+/-0.16 ms). The mean latency of the H-reflex increase (i.e., the part added to the H-reflex by up-conditioning) was 0.28+/-0.14 (+/-SE) ms greater than that of the control H-reflex. Down-conditioning had no significant effect on mean latency or duration. While these results indicate that operant conditioning does not greatly change H-reflex mean latency or duration, the effects detected with up-conditioning are consistent with the hypothesis that decreased inhibition, or increased excitation, by homonymous and heteronymous group-I oligosynaptic input contributes to the H-reflex increase produced by up-conditioning. Several other mechanisms might also account for these small effects.10aconditioning10aH-Reflex10aMemory10aplasticity10aSpinal Cord1 aWolpaw, Jonathan1 aChen, Xiang Yang  uhttp://www.ncbi.nlm.nih.gov/pubmed/1120629101999nas a2200253   4500008004100000022001400041245005300055210005100108260001200159300001200171490000800183520136000191653001701551653001301568653001101581653001501592653000801607653001101615653001601626100002101642700001301663700002101676856004801697       2001                        eng d  a0304-394000aTime course of H-reflex conditioning in the rat.0 aTime course of Hreflex conditioning in the rat  c04/2001  a85–880 v3023 aThis study sought to define the course of operantly conditioned change in the rat soleus H-reflex and to determine whether, like H-reflex conditioning and spinal stretch reflex conditioning in the monkey, it develops in distinct phases. Data from 33 rats in which the right soleus H-reflex was trained up (i.e. HRup mode) and 38 in which it was trained down (i.e. HRdown mode) were averaged to define the courses of H-reflex increase and decrease. In HRup rats, the H-reflex showed a large phase I increase within the first 2 days followed by gradual phase II increase that continued for weeks. In HRdown rats, the H-reflex appeared to show a small phase I decrease and then showed a gradual phase II decrease over weeks. In combination with other recent work, the data suggest that H-reflex conditioning begins with a rapid mode-appropriate alteration in corticospinal tract influence over the spinal arc of the H-reflex, which causes phase I change, and that the continuation of this altered influence induces gradual spinal cord plasticity that is responsible for phase II change. The results further establish the similarity of H-reflex conditioning in primates and rats. Thus, they encourage efforts to produce a single coherent model of the phenomenon based on data from the two species and indicate the potential clinical relevance of the rat data.10aconditioning10aLearning10aMemory10aplasticity10arat10aReflex10aSpinal Cord1 aChen, Xiang Yang1 aChen, Lu1 aWolpaw, Jonathan  uhttp://www.ncbi.nlm.nih.gov/pubmed/1129039301573nas a2200229   4500008004100000022001400041245004600055210004100101260001200142300001400154490000700168520098800175653001301163653001301176653001101189653002501200653001501225653001601240653001901256100002101275856004701296       1997                        eng d  a0166-223600aThe complex structure of a simple memory.0 acomplex structure of a simple memory  c12/1997  a588–5940 v203 aOperant conditioning of the vertebrate H-reflex, which appears to be closely related to learning that occurs in real life, is accompanied by plasticity at multiple sites. Change occurs in the firing threshold and conduction velocity of the motoneuron, in several different synaptic terminal populations on the motoneuron, and probably in interneurons as well. Change also occurs contralaterally. The corticospinal tract probably has an essential role in producing this plasticity. While certain of these changes, such as that in the firing threshold, are likely to contribute to the rewarded behavior (primary plasticity), others might preserve previously learned behaviors (compensatory plasticity), or are simply activity-driven products of change elsewhere (reactive plasticity). As these data and those from other simple vertebrate and invertebrate models indicate, a complex pattern of plasticity appears to be the necessary and inevitable outcome of even the simplest learning.10aH-Reflex10aLearning10aMemory10aoperant conditioning10aplasticity10aSpinal Cord10astretch reflex1 aWolpaw, Jonathan  uhttp://www.ncbi.nlm.nih.gov/pubmed/941667303032nas a2200169   4500008004100000022001400041245010100055210006900156260001200225300001600237490000700253520249700260653001602757100002102773700002102794856004702815       1997                        eng d  a0022-307700aDorsal column but not lateral column transection prevents down-conditioning of H reflex in rats.0 aDorsal column but not lateral column transection prevents downco  c09/1997  a1730–17340 v783 aOperant conditioning of the H reflex, the electrical analogue of the spinal stretch reflex, in freely moving rats is a relatively simple model for studying long-term supraspinal control over spinal cord function. Motivated by food reward, rats can gradually increase or decrease the soleus H reflex. This study is the first effort to determine which spinal cord pathways convey the descending influence from supraspinal structures that changes the H reflex. In anesthetized Sprague-Dawley rats, the entire dorsal column (DC), which includes the main corticospinal tract, or the right lateral column (LC) was transected by electrocautery. Animals recovered quickly and the minimal transient effects of transection on the right soleus H reflex disappeared within 16 days. Beginning at least 18 days after transection, 12 rats were exposed to the HRdown-conditioning mode, in which reward was given when the H reflex of the right soleus muscle was below a criterion value. In seven LC rats exposed to the HRdown mode, the H reflex fell to 71 +/- 8% (mean +/- SE) of its initial value. In six of the seven, conditioning was successful (i.e., decrease to < or = 80%). These results were comparable with those previously obtained from normal rats. In contrast, in five DC rats exposed to the HRdown mode, the H reflex at the end of exposure was 106 +/- 12% of its initial value. In none of these rats was HRdown-conditioning successful. DC rats differed significantly from normal and LC rats in both final H reflex values and number successful. In five DC and three LC rats that continued under control conditions over 30-78 days, the H reflex at the end of the period was 98 +/- 4% and 100 +/- 8%, respectively, of its initial value, indicating that DC or LC transection itself did not lead to gradual increase or decrease in the H reflex. The results indicate that the DC, containing the main corticospinal tract, is essential for HRdown-conditioning, whereas the ipsilateral LC, containing the main rubrospinal, vestibulospinal, and reticulospinal tracts, is not essential. Combined with the known muscular specificity of conditioning, these results suggest that the main corticospinal tract is essential for HRdown-conditioning. The DC ascending tract might also be necessary. The respective roles of the DC descending and ascending tracts, and transection effects on HRup-conditioning and on the maintenance of both HRup- and HRdown-conditioning after they have occurred, remain to be defined.10aSpinal Cord1 aChen, Xiang Yang1 aWolpaw, Jonathan  uhttp://www.ncbi.nlm.nih.gov/pubmed/931045801790nas a2200229   4500008004100000022001400041245005800055210005600113260001200169300001200181490000800193520117500201653001301376653002501389653001501414653000801429653001801437653001601455100002101471700002101492856004701513       1996                        eng d  a0014-481900aReversal of H-reflex operant conditioning in the rat.0 aReversal of Hreflex operant conditioning in the rat  c11/1996  a58–620 v1123 aIn response to an operant conditioning task, rats can gradually increase or decrease soleus H-reflex amplitude without change in background electromyographic activity or M response amplitude. Both increase (under the HRup mode) and decrease (under the HRdown mode) develop over weeks. The present study investigated reversal of conditioned H-reflex change. Following collection of control data, rats were exposed to one mode (HRup or HRdown) for 50 days, and then exposed to the opposite mode for up to 72 days. Rats responded to each mode exposure with gradual, mode-appropriate change in H-reflex amplitude. This finding is consistent with other evidence that H-reflex conditioning depends on spinal cord plasticity. The effects of exposure to the HRup (or HRdown) mode were not affected by whether exposure followed previous exposure to the HRdown (or HRup) mode. In accord with recent studies suggesting that HRup and HRdown conditioning have different spinal mechanisms, these results suggest that reversal of H-reflex change is due primarily to the superimposition of additional plasticity rather than to decay of the plasticity responsible for the initial change.10aH-Reflex10aoperant conditioning10aplasticity10arat10asoleus muscle10aSpinal Cord1 aChen, Xiang Yang1 aWolpaw, Jonathan  uhttp://www.ncbi.nlm.nih.gov/pubmed/895140702025nas a2200169   4500008004100000022001400041245006000055210005800115260001200173300001400185490000700199520154400206653001601750100002101766700002101787856004701808       1995                        eng d  a0022-307700aOperant conditioning of H-reflex in freely moving rats.0 aOperant conditioning of Hreflex in freely moving rats  c01/1995  a411–4150 v733 a1. Primates can increase or decrease the spinal stretch reflex and its electrical analogue, the H-reflex (HR), in response to an operant conditioning task. This conditioning changes the spinal cord itself and thereby provides an experimental model for defining the processes and substrates of a learned change in behavior. Because the phenomenon has been demonstrated only in primates, its generality and theoretical implications remain unclear, and its experimental use is restricted by the difficulties of primate research. In response to these issues, the present study explored operant conditioning of the H-reflex in the rat. 2. Seventeen Sprague-Dawley rats implanted with chronic electromyographic (EMG) recording electrodes in one soleus muscle and nerve cuff stimulating electrodes on the posterior tibial nerve were rewarded (either with medial forebrain bundle stimulation or food) for increasing (HRup conditioning mode) or decreasing (HRdown conditioning mode) soleus H-reflex amplitude without change in background EMG or M response (direct muscle response) amplitude. 3. H-reflex amplitude changed appropriately over 3-4 wk. Under the HRup mode, it rose to an average of 158 +/- 54% (mean +/- SD) of initial value, whereas under the HRdown mode it fell to an average of 67 +/- 11% of initial value. Background EMG and M response amplitude did not change. 4. Operant conditioning of the H-reflex in the rat appears similar in rate and final magnitude of change to that observed in the monkey.(ABSTRACT TRUNCATED AT 250 WORDS)10aSpinal Cord1 aChen, Xiang Yang1 aWolpaw, Jonathan  uhttp://www.ncbi.nlm.nih.gov/pubmed/771458402070nas a2200241   4500008004100000022001400041245009400055210006900149260001200218300001600230490000700246520139200253653001701645653001301662653001101675653001801686653001501704653001201719653001601731653001301747100002101760856004701781       1994                        eng d  a0195-913100aAcquisition and maintenance of the simplest motor skill: investigation of CNS mechanisms.0 aAcquisition and maintenance of the simplest motor skill investig  c12/1994  a1475–14790 v263 aThe spinal stretch reflex (SSR), or tendon jerk, is the simplest behavior of the vertebrate nervous system. It is mediated primarily by a wholly spinal, two-neuron pathway. Recent studies from several laboratories have shown that primates, human and nonhuman, can gradually increase or decrease the size of the SSR when reward depends on such change. Evidence of this training remains in the spinal cord after all supraspinal influence is removed. Thus, the learning of this simple motor skill changes the spinal cord itself. Comparable spinal plasticity probably plays a role in the acquisition of many complex motor skills. Intracellular physiological and anatomical studies are seeking the location and nature of this spinal cord plasticity. Attention focuses on the most probable sites of change, the group Ia afferent synapse on the alpha motoneuron and the motoneuron itself. Results to date indicate that modifications are present at several places in the spinal cord. Current clinical studies are investigating the use of spinal cord adaptive plasticity as a basis for a new therapeutic approach to spasticity and other forms of abnormal spinal reflex function that result from spinal cord injury, stroke, or other neurological disorders. In the future, understanding of spinal reflex plasticity may lead to development of improved training methods for a variety of motor skills.10aconditioning10aLearning10aMemory10aMotor control10aplasticity10aprimate10aSpinal Cord10atraining1 aWolpaw, Jonathan  uhttp://www.ncbi.nlm.nih.gov/pubmed/786988203248nas a2200169   4500008004100000022001400041245006900055210006800124260001200192300001400204490000800218520275000226653001602976100001802992700002103010856004703031       1994                        eng d  a0021-996700aSynaptic terminal coverage of primate triceps surae motoneurons.0 aSynaptic terminal coverage of primate triceps surae motoneurons  c07/1994  a345–3580 v3453 aThis study examined the synaptic terminal coverage of primate triceps surae (TS) motoneurons at the electron microscopic level. In three male pigtail macaques, motoneurons were labeled by retrograde transport of cholera toxin-horseradish peroxidase that was injected into TS muscles bilaterally and visualized with tetramethylbenzidine stabilized with diaminobenzidine. Somatic, proximal dendritic, and distal dendritic synaptic terminals were classified by standard criteria and measured. Overall and type-specific synaptic terminal coverages and frequencies were determined. Labeled cells were located in caudal L5 to rostral S1 ventral horn and ranged from 40 to 74 microns in diameter (average, 54 microns). The range and unimodal distribution of diameters, the label used, and the presence of C terminals on almost all cells indicated that the 15 cell bodies and associated proximal dendrites analyzed here probably belonged to alpha-motoneurons. Synaptic terminals covered 39% of the cell body membrane, 60% of the proximal dendritic membrane, and 40% of the distal dendritic membrane. At each of these three sites, F terminals (flattened or pleomorphic vesicles, usually symmetric active zones, average contact length 1.6 microns) were most common, averaging 52%, 56%, and 58% of total coverage and 56%, 57%, and 58% of total number of cell bodies, proximal dendrites, and distal dendrites respectively. S terminals (round vesicles, usually asymmetric active zones, average contact length 1.3 microns) averaged 24%, 29%, and 33% of coverage and 33%, 35%, and 36% of number at these three sites, respectively. Thus, S terminals were slightly more prominent relative to F terminals on distal dendrites than on cell bodies. C terminals (spherical vesicles, subsynaptic cisterns associated with rough endoplasmic reticulum, average contact length 3.5 microns) constituted 24% and 11% of total terminal coverage on cell bodies and proximal dendrites, respectively, and averaged 11% and 6% of terminal number at these two locations. M terminals (spherical vesicles, postsynaptic Taxi bodies, some with presynaptic terminals, average contact length 2.7 microns) were absent on cell bodies and averaged 3% and 7% of total coverage and 2% and 5% of terminals on proximal and distal dendrites, respectively. Except for M terminals, which tended to be smaller distally, terminal contact length was not correlated with location. Total and type-specific coverages and frequencies were not correlated with cell body diameter. Primate TS motoneurons are similar to cat TS motoneurons in synaptic terminal morphology, frequency, and distribution. However, primate terminals appear to be smaller, so that the fraction of membrane covered by them is lower.10aSpinal Cord1 aStarr, K., A.1 aWolpaw, Jonathan  uhttp://www.ncbi.nlm.nih.gov/pubmed/792990603311nas a2200229   4500008004100000022001400041245009200055210006900147260001200216300001400228490000800242520262900250653002202879653001402901653002702915653002102942653001302963653001602976100002102992700002103013856004703034       1994                        eng d  a0021-996700aTriceps surae motoneuron morphology in the rat: a quantitative light microscopic study.0 aTriceps surae motoneuron morphology in the rat a quantitative li  c05/1994  a143–1570 v3433 aThe rat is now the model of choice for many studies of motor function. However, little quantitative information on the structure of rat motoneurons is available. In conjunction with efforts to define the physiologic and anatomic substrates of operantly conditioned plasticity in the spinal cord, 13 physiologically identified triceps surae motoneurons in the rat lumbar spinal cord were labeled intracellularly with horseradish peroxidase and completely reconstructed and measured with a computer-based neuron-tracing system. Somata were all located in the ventral horn of lumbar segments 4-5, had an average diameter of 35 microns, and had 6-12 dendrites. Dendrites ramified throughout the ventral horn and also penetrated the white matter. Their spread was greater in the rostrocaudal and dorsoventral directions (1.53 +/- 0.24 mm and 1.35 +/- 0.23 mm, respectively) than in the mediolateral direction (0.85 +/- 0.14 mm). Regardless of soma location, dendritic fields usually extended throughout the ipsilateral coronal cross-section of the ventral horn. As a result, the ventral or lateral extent of the field was correlated strongly with the soma's distance from the ventral or lateral border, respectively, of the ventral horn. Furthermore, although soma locations in the coronal plane varied widely, the centers of the dendritic fields tended to cluster near the center of the ventral horn. Dendrites constituted 96.2-98.4% (mean +/- SD = 97.3 +/- 0.7%) of the total neuronal surface area. Each of the 104 dendrites studied had an average of 13 branch points and 27 segments. First-order segment diameters ranged from 1.4 to 11.7 microns (mean +/- SD = 5.3 +/- 2.1 microns). Total dendritic length, surface area, volume, number of dendritic segments, and maximum segment order were correlated strongly with diameter of the first-order segment. Proceeding distally between branch points, the mean decrease in dendritic diameter (i.e., tapering) +/- the standard deviation was 22 +/- 8% of the proximal diameter. The average ratio +/- the standard deviation of the sum of the average diameters of each daughter segment raised to the 1.5 power to the average diameter of the parent segment raised to the 1.5 power (i.e., Rall's ratio; Rall, 1959) was 0.87 +/- 0.08. In comparison with cat alpha-motoneurons, rat motoneurons had smaller soma diameters, fewer dendrites, smaller total surface areas, and shorter total dendritic lengths. However, the number of terminations per dendrite was similar in the two species, so that rat motoneurons had more terminations per unit dendritic length.(ABSTRACT TRUNCATED AT 400 WORDS)10acomputer assisted10adendrites10ahorseradish peroxidase10aimage processing10aSoftware10aSpinal Cord1 aChen, Xiang Yang1 aWolpaw, Jonathan  uhttp://www.ncbi.nlm.nih.gov/pubmed/802743200429nas a2200157   4500008004100000022001400041245004000055210003900095260000900134300001400143490000700157653001600164100002100180700002300201856004700224       1993                        eng d  a0091-395200aAdaptive plasticity in spinal cord.0 aAdaptive plasticity in spinal cord  c1993  a163–1740 v5910aSpinal Cord1 aWolpaw, Jonathan1 aCarp, Jonathan, S.  uhttp://www.ncbi.nlm.nih.gov/pubmed/842010302325nas a2200229   4500008004100000022001400041245009300055210006900148260001200217300001200229490000700241520165100248653001301899653001101912653002501923653001501948653001601963100002101979700002502000700002302025856004702048       1993                        eng d  a0014-481900aOperant conditioning of the primate H-reflex: factors affecting the magnitude of change.0 aOperant conditioning of the primate Hreflex factors affecting th  c12/1993  a31–390 v973 aPrimates can gradually increase or decrease H-reflex amplitude in one leg when reward depends on that amplitude. The magnitude of change varies greatly from animal to animal. This study sought to define the factors that control this magnitude. It evaluated the influence of animal age, muscle size (absolute and relative), background electromyographic activity (EMG) level, M response amplitude, initial H-reflex amplitude, performance intensity, and behavior of the contralateral leg. Fifty-four animals (Macaca nemestrina) underwent operant conditioning of the triceps surae H-reflex in one leg (the trained leg). Twenty-eight were rewarded for larger H-reflexes (HRup animals), and 26 were rewarded for smaller H-reflexes (HRdown animals). In the HRup animals, H-reflex amplitude in the trained leg rose to an average final value of 177% of its initial amplitude. Magnitude of increase varied widely across animals. Nine animals rose to 120-140%, 11 to 160-240%, three to 300% or more, and five remained within 20% of initial amplitude. In the HRdown animals, H-reflex amplitude in the trained leg decreased to an average of 69% of initial amplitude. Magnitude of decrease varied widely. Five animals decreased to 20-40%, seven to 40-60%, six to 60-80%, and eight remained within 20% of initial amplitude. Animal age, as assessed by weight, markedly affected HRdown conditioning, but not HRup conditioning. Heavy HRdown animals (> or = 6 kg) were more successful than light HRdown animals (< 6 kg). Thirteen of 14 heavy animals and only five of 12 light animals decreased to less than 80% of initial amplitude.(ABSTRACT TRUNCATED AT 250 WORDS)10aH-Reflex10amonkey10aoperant conditioning10aplasticity10aSpinal Cord1 aWolpaw, Jonathan1 aHerchenroder, P., A.1 aCarp, Jonathan, S.  uhttp://www.ncbi.nlm.nih.gov/pubmed/813183001213nas a2200313   4500008004100000022001400041245005000055210004500105300001400150490000700164520043400171653001300605653001000618653001700628653002100645653001300666653001100679653001500690653001100705653001200716653001100728653001600739653001600755653002200771653001500793100002100808700002300829856004700852       1993                        eng d  a0065-140000aThe volitional nature of the simplest reflex.0 avolitional nature of the simplest reflex  a103–1110 v533 aRecent studies suggest that none of the behaviors of the vertebrate CNS are fixed responses incapable of change. Even the simplest reflex of all, the two-neuron, monosynaptic spinal stretch reflex (SSR), undergoes adaptive change under appropriate circumstances. Operantly conditioned SSR change occurs gradually over days and weeks and is associated with a complex pattern of CNS plasticity at both spinal and supraspinal sites.10abehavior10aBrain10aconditioning10ahuman physiology10aLearning10aMemory10amotoneuron10anature10aprimate10aReflex10aSpinal Cord10aspinal site10asupra spinal site10avertebrate1 aWolpaw, Jonathan1 aCarp, Jonathan, S.  uhttp://www.ncbi.nlm.nih.gov/pubmed/831723802960nas a2200157   4500008004100000022001400041245006000055210005900115260001200174300001600186490000700202520250700209653001602716100002302732856004702755       1992                        eng d  a0022-307700aPhysiological properties of primate lumbar motoneurons.0 aPhysiological properties of primate lumbar motoneurons  c10/1992  a1121–11320 v683 a1. Intracellular recordings were obtained from 149 motoneurons innervating triceps surae (n = 109) and more distal muscles (n = 40) in 14 pentobarbital-anesthetized monkeys (Macaca nemestrina). The variables evaluated were resting membrane potential, action potential amplitude, conduction velocity (CV), input resistance (RN), membrane time constant (tau m), electrotonic length (L), whole-cell capacitance (Ctot), long current pulse threshold (rheobase), short current pulse threshold (Ishort), afterhyperpolarization (AHP) maximum amplitude (AHPmax), AHP duration (AHPdur), time to half maximum AHP amplitude (AHP t1/2), depolarization from resting potential to elicit action potential (Vdep), and threshold voltage for action potential discharge (Vthr). 2. Mean values +/- SD for the entire sample of motoneurons are as follows: resting membrane potential -67 +/- 6 mV; action potential amplitude 75 +/- 7 mV; CV 71 +/- 6 m/s; RN 1.0 +/- 0.5 M omega; tau m 4.4 +/- 1.5 ms; L 1.4 +/- 0.2 lambda; Ctot 7.1 +/- 1.8 nF; rheobase 13 +/- 7 nA; Ishort 29 +/- 14 nA; AHPmax 3.5 +/- 1.3 mV; AHPdur 77 +/- 26 ms; AHP t 1/2 21 +/- 7 ms; Vdep 11 +/- 4 mV; and Vthr -56 +/- 5 mV. CV is lower in soleus than in either medial or lateral gastrocnemius motoneurons, and RN is lower and tau m is longer in soleus than in lateral gastrocnemius motoneurons. 3. RN is higher in motoneurons with longer tau m and slower CV. A linear relationship exists between log(CV) and log(1/RN) with a slope of 1.8-2.2 (depending on the action potential amplitude acceptance criteria used), suggesting that membrane resistivity (Rm) does not vary systematically with cell size. 4. Rheobase is higher in motoneurons with lower RN, longer tau m, shorter AHP time course, and higher CV. Ishort and normalized rheobase (i.e., rheobase/Ctot) vary similarly with these motoneuron properties, except that Ishort is independent of tau m and normalized rheobase is independent of CV. 5. Vthr tends to be more depolarized in motoneurons with large Ctot, but the relationship is sufficiently weak so that any systematic variation in Vthr according to cell size probably contributes only minimally to recruitment order. Vthr does not vary systematically with CV, AHP time course, RN, or tau m. 6. Quantitative differences between macaque and cat triceps surae motoneurons are apparent in CV, which is slower in macaque than in cat, and to a lesser extent in tau m and RN, which are lower in macaque than in cat.(ABSTRACT TRUNCATED AT 400 WORDS)10aSpinal Cord1 aCarp, Jonathan, S.  uhttp://www.ncbi.nlm.nih.gov/pubmed/143207202723nas a2200241   4500008004100000022001400041245010800055210006900163260001200232300001400244490000700258520200700265653002702272653000802299653001102307653001502318653002502333653001602358100002302374700001902397700001802416856004702434       1991                        eng d  a0014-481900aAlterations in motoneuron properties induced by acute dorsal spinal hemisection in the decerebrate cat.0 aAlterations in motoneuron properties induced by acute dorsal spi  c02/1991  a539–5480 v833 aUsing intracellular recording techniques, we studied the response characteristics of two separate populations of triceps surae motoneurons in unanesthetized decerebrate cats, recorded before and after low thoracic hemisection of the spinal cord. In each preparation, we studied the response properties of one group of motoneurons and the protocol was then repeated for a separate group, immediately following the dorsal hemisection. In each group, we examined both the minimum firing rates of motoneurons during intracellular current injection and a range of cellular properties, including input resistance, rheobase current and afterhyperpolarization time course and magnitude. Although earlier studies from this laboratory have shown substantial reductions in minimum firing rate in reflexively active motoneurons in the hemisected decerebrated preparation, the response of motoneurons to intracellular current injection in the current preparation proved to be quite different. Minimum firing rates were either normal or even somewhat higher in the post-lesion group, while the time course of the afterhyperpolarization was shortened. Moreover, these effects were not evenly distributed across the motoneuron pool. The rate effect was most evident in motoneurons with higher conduction velocity, while the afterhyperpolarization effect occurred predominantly in motoneurons with lower conduction velocity. Neither of these effects could be accounted for by lesion-induced changes in other cellular properties. We conclude that tonically active neurons with descending axons traversing dorsolateral white matter may influence both the discharge characteristics and membrane properties of spinal motoneurons in novel ways, presumably by modifying voltage or calcium activated motoneuronal conductances. The previously described reactions in the firing rate of motoneurons after such lesions appear to be mediated by different means, perhaps by alterations in synaptic input from segmental interneurons.10aafterhyperpolarization10acat10alesion10amotoneuron10arepetitive discharge10aSpinal Cord1 aCarp, Jonathan, S.1 aPowers, R., K.1 aRymer, W., Z.  uhttp://www.ncbi.nlm.nih.gov/pubmed/202619601079nas a2200181   4500008004100000022001400041245005300055210005200108260001200160300001400172490000800186520058000194653001600774100002100790700001600811700002300827856004700850       1991                        eng d  a0077-892300aOperantly conditioned plasticity in spinal cord.0 aOperantly conditioned plasticity in spinal cord  c08/1991  a338–3480 v6273 aRecent work has shown that the monosynaptic pathway of the SSR can be operantly conditioned, and that a significant part of the plasticity responsible for the behavioral change resides in the spinal cord. The most likely sites of this activity-driven plasticity are the synapse of the Ia afferent neuron on the motoneuron and/or the motoneuron itself. Because the SSR pathway is the simplest and most accessible stimulus-response pathway in the vertebrate CNS, it may provide a valuable experimental model for elucidating activity-driven CNS changes responsible for learning.10aSpinal Cord1 aWolpaw, Jonathan1 aLee, C., L.1 aCarp, Jonathan, S.  uhttp://www.ncbi.nlm.nih.gov/pubmed/188314301104nas a2200169   4500008004100000022001400041245003400055210003300089260001200122300001400134490000700148520067200155653001600827100002100843700002300864856004700887       1990                        eng d  a0166-223600aMemory traces in spinal cord.0 aMemory traces in spinal cord  c04/1990  a137–1420 v133 aThe complexity and inaccessibility of the vertebrate CNS impede the localization and description of memory traces and the definition of the processes that create them. Recent work has shown that the spinal stretch reflex (SSR), which is produced by a monosynaptic two-neuron pathway, can be operantly conditioned, and that memory traces responsible for this behavioral change reside in the spinal cord. The probable locations are the terminal of the Ia affernt neuron on the motoneuron and/or the motoneuron itself. Because it modifies a simple well-defined and accessible pathway, SSR conditioning may be a valuable experimental model for studying vertebrate memory.10aSpinal Cord1 aWolpaw, Jonathan1 aCarp, Jonathan, S.  uhttp://www.ncbi.nlm.nih.gov/pubmed/169217001922nas a2200169   4500008004100000022001400041245010600055210006900161260001200230300001200242490000700254520139200261653001601653100001501669700002101684856004701705       1989                        eng d  a0013-469400aDiurnal rhythms in primate spinal reflexes and accompanying cortical somatosensory evoked potentials.0 aDiurnal rhythms in primate spinal reflexes and accompanying cort  c01/1989  a69–800 v723 aWe recorded spinal reflexes and cortical somatosensory evoked potentials (SEPs), elicited by stretching the biceps or the triceps muscle or by electrically stimulating the posterior tibial nerve, from monkeys throughout the day. Amplitudes of the spinal stretch reflex (SSR) and of its electrically evoked analogue, the H-reflex, varied diurnally: both were greatest midway through the lights-off period and smallest during the lights-on period. Stretch-evoked and electrically evoked SEP amplitudes also varied diurnally, but were out of phase with the spinal reflex rhythms. The H-reflex is elicited by direct stimulation of the nerve and thus, unlike the SSR, bypasses the muscle spindle. The H-reflex diurnal rhythm and the phase difference between the spinal reflex and SEP diurnal rhythms indicate that these rhythms are mediated at least in part by central mechanisms. Furthermore, both the spinal reflex and SEP diurnal rhythms appeared to be entrained by the light-dark cycle, which suggests that they may be coupled to the same oscillator. Besides their theoretical importance, these rhythms have important implications for experimental and clinical studies of spinal reflexes and SEPs. These rhythms are especially pertinent to the interpretation of long-term monitoring studies, as are often carried out in the Intensive Care Unit and during lengthy neurosurgical procedures.10aSpinal Cord1 aDowman, R.1 aWolpaw, Jonathan  uhttp://www.ncbi.nlm.nih.gov/pubmed/246447703194nas a2200169   4500008004100000022001400041245008700055210006900142260001200211300001400223490000700237520268000244653001602924100002102940700001602961856004702977       1989                        eng d  a0022-307700aMemory traces in primate spinal cord produced by operant conditioning of H-reflex.0 aMemory traces in primate spinal cord produced by operant conditi  c03/1989  a563–5720 v613 a1. Study of memory traces in higher animals requires experimental models possessing well-localized and technically accessible memory traces–plasticity responsible for behavioral change, not dependent on control from elsewhere, and open to detailed investigation. Our purpose has been to develop such a model based on the wholly spinal, largely monosynaptic path of the spinal stretch reflex. Previous studies described operant conditioning of this reflex and of its electrical analog, the H-reflex. In this study, we sought to determine whether conditioning causes changes in the spinal cord that affect the reflex and are not dependent on continued supraspinal influence, and thus qualify as memory traces. 2. Sixteen monkeys underwent chronic conditioning of the triceps surae H-reflex. Eight were rewarded for increasing H-reflex amplitude (HR increases mode), and eight were rewarded for decreasing it (HR decreases mode). In each animal, the other leg was an internal control. Over several months of conditioning, H-reflex amplitude in the conditioned leg rose in HR increases animals and fell in HR decreases animals. H-reflex amplitude in the control leg changed little. 3. After HR increases or HR decreases conditioning, each animal was deeply anesthetized and surgically prepared. The reflex response to supramaximal dorsal root stimulation was measured from the triceps surae nerve as percent of response to supramaximal ventral root stimulation, which was the maximum possible response. Data from both legs were collected before and for up to 3 days after thoracic (T9-10) cord transection. The animal remained deeply anesthetized throughout and was killed by overdose. 4. The reflex asymmetries produced by conditioning were still present several days after transection removed supraspinal influence: reflexes of HR increases animals were significantly larger in HR increases legs than in control legs and reflexes of HR decreases animals were significantly smaller in HR decreases legs than in control legs. 5. Reflex amplitude was much greater in the control legs of anesthetized HR decreases animals than in the control legs of anesthetized HR increases animals. 6. Chronic conditioning had at least two effects on the spinal cord. The first effect, task-appropriate reflex asymmetry, was evident both in the awake behaving animal and in the anesthetized transected animal. The second effect, larger control leg reflexes in HR decreases than in HR increases animals, was evident only in the anesthetized animal. By removing supraspinal control, anesthesia and transection revealed a previously hidden effect of conditioning.(ABSTRACT TRUNCATED AT 400 WORDS)10aSpinal Cord1 aWolpaw, Jonathan1 aLee, C., L.  uhttp://www.ncbi.nlm.nih.gov/pubmed/270910001794nas a2200253   4500008004100000022001400041245008600055210006900141260001200210300001200222490000700234520107100241653001301312653001101325653002401336653002501360653001501385653001601400653001801416100002101434700001601455700002201471856004701493       1989                        eng d  a0014-481900aOperant conditioning of primate triceps surae H-reflex produces reflex asymmetry.0 aOperant conditioning of primate triceps surae Hreflex produces r  c03/1989  a35–390 v753 aMonkeys are able to increase or decrease triceps surae H-reflex when reward depends on reflex amplitude. Operantly conditioned change occurs over weeks and produces persistent alterations in the lumbosacral spinal cord which should be technically accessible substrates of primate memory. Previous work monitored and conditioned triceps surae H-reflex in one leg. To determine whether H-reflex conditioning in one leg affects the control leg, the present study monitored H-reflexes in both legs while the reflex in one leg underwent HR increases or HR decreases conditioning. Under the HR increases mode, H-reflex increase was much greater in the HR increases leg than in the control leg. Under the HR decreases mode, H-reflex decrease was confined to the HR decreases leg. By showing that conditioning of one leg's H-reflex produces H-reflex asymmetry, the data further define the phenomenon and indicate that the other leg can serve as an internal control for physiologic and anatomic studies exploring the sites and mechanisms of the spinal cord memory substrates.10aLearning10aMemory10amonosynaptic reflex10aoperant conditioning10aplasticity10aSpinal Cord10aspinal reflex1 aWolpaw, Jonathan1 aLee, C., L.1 aCalaitges, J., G.  uhttp://www.ncbi.nlm.nih.gov/pubmed/270735401941nas a2200181   4500008004100000022001400041245014000055210006900195260001200264300001600276490000800292520134000300653001601640100002301656700001301679700002001692856004701712       1989                        eng d  a0022-356500aPrevention of phencyclidine-induced depression of the segmental reflex by L-3,4-dihydroxyphenylalanine in the rat spinal cord in vitro.0 aPrevention of phencyclidineinduced depression of the segmental r  c03/1989  a1048–10530 v2483 aThe interaction between phencyclidine (PCP) and the catecholamine precursor L-3,4-dihydroxyphenylalanine (DOPA) was studied in the isolated spinal cord from neonatal rats. PCP decreased the magnitude of the dorsal-ventral reflex and enhanced frequency-dependent depression of the reflex in a concentration-dependent manner. Although DOPA and DL-threo-3,4-dihydroxyphenylserine (a direct precursor for norepinephrine) had no effect on the reflex by themselves, DOPA, but not DL-threo-3,4-dihydroxyphenylserine prevented the depression of the reflex response by PCP in a concentration-dependent manner. Inhibition of aromatic-L-amino-acid decarboxylase (EC 4.1.1.2A) by m-hydroxybenzylhydrazine markedly attenuated the action of DOPA in preventing the depression caused by PCP. The dopamine receptor antagonists haloperidol and chlorpromazine blocked the action of DOPA, but the alpha and beta adrenergic receptor antagonists phentolamine and timolol, respectively, did not. In addition, prior treatment of neonatal rats with 6-hydroxydopamine diminished the ability of DOPA to prevent the depressant effect of PCP whereas partially attenuating the depressant effect of PCP alone. These results suggest that DOPA attenuated PCP-induced depression of spinal cord transmission through its conversion to dopamine rather than norepinephrine.10aSpinal Cord1 aCarp, Jonathan, S.1 aOhno, Y.1 aWarnick, J., E.  uhttp://www.ncbi.nlm.nih.gov/pubmed/249535001361nas a2200229   4500008004100000022001400041245010600055210006900161260001200230300001400242490000700256520067400263653002400937653001200961653001600973653002300989653001801012653001701030100002101047700001601068856004701084       1987                        eng d  a0014-481900aMotoneuron response to dorsal root stimulation in anesthetized monkeys after spinal cord transection.0 aMotoneuron response to dorsal root stimulation in anesthetized m  c10/1987  a428–4330 v683 aIn preparation for studying the spinal cord alterations produced by operant conditioning of spinal reflexes, we studied peripheral nerve responses to supramaximal dorsal root stimulation in the lumbosacral cord of deeply anesthetized monkeys before and after thoracic cord transection. Except for variable depression in the first few minutes, reflex responses were not reduced or otherwise significantly affected by transection in the hour immediately following the lesion or for at least 50 h. The results suggest that reduction in muscle spindle sensitivity and/or in polysynaptic motoneuron excitation contributes to stretch reflex depression after cord transection.10amonosynaptic reflex10aprimate10aSpinal Cord10aspinal cord injury10aspinal reflex10aspinal shock1 aWolpaw, Jonathan1 aLee, C., L.  uhttp://www.ncbi.nlm.nih.gov/pubmed/348023303121nas a2200157   4500008004100000022001400041245006700055210006400122260001200186300001400198490000700212520266000219653001602879100002102895856004702916       1987                        eng d  a0022-307700aOperant conditioning of primate spinal reflexes: the H-reflex.0 aOperant conditioning of primate spinal reflexes the Hreflex  c02/1987  a443–4590 v573 aThe study of primate memory substrates, the CNS alterations which preserve conditioned responses, requires an experimental model that fulfills two criteria. First, the essential alterations must be in a technically accessible location. Second, they must persist without input from other CNS regions. The spinal cord is the most technically accessible and readily isolated portion of the primate CNS. Recent work has demonstrated that the spinal stretch reflex (SSR), the initial, wholly segmental response to muscle stretch, can be operantly conditioned and suggests that this conditioning may produce persistent spinal alteration. The present study attempted similar operant conditioning of the H-reflex, the electrical analog of the SSR. The primary goals were to demonstrate that spinal reflex conditioning can occur even if the muscle spindle is removed from the reflex arc and to demonstrate conditioning in the lumbosacral cord, which is far preferable to the cervical cord for future studies of neuronal and synaptic mechanisms. Nine monkeys prepared with chronic fine-wire triceps surae (gastrocnemius and soleus) electromyographic (EMG) electrodes were taught by computer to maintain a given level of background EMG activity. At random times, a voltage pulse just above M response (direct muscle response) threshold was delivered to the posterior tibial nerve via a chronically implanted silicon nerve cuff and elicited the triceps surae H-reflex. Under the control mode, reward always followed. Under the HR increases or HR decreases mode, reward followed only if the absolute value of triceps surae EMG from 12 to 22 ms after the pulse (the H-reflex interval) was above (HR increases) or below (HR decreases) a set value. Monkeys completed 3,000-6,000 trials/day over study periods of 2-3 mo. Background EMG and M response amplitude remained stable throughout data collection. H-reflex amplitude remained stable under the control mode. Under the HR increases mode (5 animals) or HR decreases mode (4 animals), H-reflex amplitude (EMG amplitude in the H-reflex interval minus background EMG amplitude) changed appropriately over at least 6 wk. Change appeared to occur in two phases: an abrupt change within the first day, followed by slower change, which continued indefinitely. Change occurred in all three triceps surae muscles (medial and lateral gastrocnemii and soleus). Under the HR increases mode, H-reflex amplitude rose to an average of 213% of control, whereas under the HR decreases mode it fell to an average of 68% of control. The results demonstrate that the H-reflex can be operantly conditioned.(ABSTRACT TRUNCATED AT 400 WORDS)10aSpinal Cord1 aWolpaw, Jonathan  uhttp://www.ncbi.nlm.nih.gov/pubmed/355968702150nas a2200193   4500008004100000022001400041245007100055210006900126260001200195300001400207490000700221520158500228653001601813100002101829700002001850700001901870700002001889856004701909       1986                        eng d  a0022-307700aAdaptive plasticity in primate spinal stretch reflex: persistence.0 aAdaptive plasticity in primate spinal stretch reflex persistence  c02/1986  a272–2790 v553 aMonkeys can gradually change the amplitude of the wholly segmental, largely monosynaptic, spinal stretch reflex (SSR) when confronted by a task requiring such change (15-19). Change develops over months and may reverse and redevelop at similarly slow rates. We investigated the persistence of SSR amplitude change over nonperformance periods of up to 38 days. Eight animals with chronic EMG electrodes learned to maintain elbow angle and a given level of biceps background EMG against constant extension torque. At random times, a brief additional extension torque pulse elicited the biceps SSR. In the control mode, reward always followed. Under the SSR increase or SSR decrease mode, reward occurred only if the absolute value of biceps EMG in the SSR interval was above or below a set value. Animals completed 3,000-6,000 trials/day over data-collection periods of 2-17 mo. Animals worked first under the control mode for up to 60 days and then under the SSR increase or SSR decrease mode for up to 274 days. Mode was switched once or twice more (SSR increase to SSR decrease or vice versa) over subsequent months. Animals responded to each SSR increase or SSR decrease mode exposure with gradual mode-appropriate change in SSR amplitude. Mode exposures were interrupted by gaps in performance of 10-38 days. Gaps produced transient 10- to 15% decreases in SSR amplitude under the control mode. This nonspecific decrease disappeared over the first week of postgap performance. Under the control mode, gaps had no other effects on SSR amplitude.(ABSTRACT TRUNCATED AT 250 WORDS)10aSpinal Cord1 aWolpaw, Jonathan1 aO'Keefe, J., A.1 aNoonan, P., A.1 aSanders, M., G.  uhttp://www.ncbi.nlm.nih.gov/pubmed/395069101802nas a2200217   4500008004100000022001400041245009300055210006900148260001200217300001400229490000700243520113900250653003101389653001401420653001601434653001901450653002701469100002301496700001801519856004701537       1986                        eng d  a0014-481900aEnhancement by serotonin of tonic vibration and stretch reflexes in the decerebrate cat.0 aEnhancement by serotonin of tonic vibration and stretch reflexes  c03/1986  a111–1220 v623 aThe effects of pharmacological manipulation of serotonergic systems on spinal reflexes were determined in the unanesthetized decerebrate cat. The prolonged motor output that continues after cessation of high frequency longitudinal tendon vibration was strongly enhanced by the serotonin reuptake blocker fluoxetine and the serotonin precursor 5-hydroxytryptophan, and was decreased by the serotonin receptor antagonist methysergide. In addition, both dynamic and static stretch reflex stiffness was markedly increased by fluoxetine and 5-hydroxytryptophan, while methysergide produced a decrease in stretch reflex stiffness. These powerful effects on tonic vibration and stretch reflexes could not be explained by drug-induced alterations in muscle spindle primary afferent discharge. In light of other recent results on serotonin-mediated effects on motoneurons, we believe that the effects of these agents result from modification of an intrinsically mediated prolonged depolarization of spinal neurons. However, the possibility that these drugs modify longlasting discharge in associated interneuronal pathways cannot be ruled out.10abistable neuronal behavior10aserotonin10aSpinal Cord10astretch reflex10atonic vibration reflex1 aCarp, Jonathan, S.1 aRymer, W., Z.  uhttp://www.ncbi.nlm.nih.gov/pubmed/300719101682nas a2200181   4500008004100000022001400041245010400055210006900159260001200228300001600240490000700256520111400263653001601377100002101393700001901414700002001433856004701453       1983                        eng d  a0022-307700aAdaptive plasticity in primate spinal stretch reflex: behavior of synergist and antagonist muscles.0 aAdaptive plasticity in primate spinal stretch reflex behavior of  c12/1983  a1312–13190 v503 aMonkeys can gradually change the amplitude of the biceps spinal stretch reflex (SSR) without change in initial muscle length or biceps background electromyographic activity (EMG) (17). We investigated the concurrent behavior of synergist (brachialis and brachioradialis) and antagonist (triceps) muscles. Synergist background EMG remained stable while marked change occurred in biceps SSR amplitude. Triceps background EMG was minimal under all conditions. Thus biceps SSR amplitude change was not due to change in the background activity of closely related muscles. When biceps SSR amplitude changed, synergist SSR amplitude changed similarly but to a lesser extent. Brachialis change averaged 72% of biceps change, while brachioradialis change averaged 33%. By indicating that SSR amplitude change is relatively specific to the agonist muscle, this finding eliminates a number of nonspecific mechanisms as possible origins of SSR amplitude change. Thus it supports the potential value of the SSR as a system for studying the neuronal and synaptic bases of memory in the primate central nervous system (CNS).10aSpinal Cord1 aWolpaw, Jonathan1 aSeegal, R., F.1 aO'Keefe, J., A.  uhttp://www.ncbi.nlm.nih.gov/pubmed/666332802956nas a2200181   4500008004100000022001400041245007900055210006900134260001200203300001600215490000700231520241200238653001602650100002102666700002102687700001902708856004702727       1983                        eng d  a0022-307700aAdaptive plasticity in primate spinal stretch reflex: initial development.0 aAdaptive plasticity in primate spinal stretch reflex initial dev  c12/1983  a1296–13110 v503 aDescription of the neuronal and synaptic bases of memory in the vertebrate central nervous system (CNS) requires a CNS stimulus-response pathway that is defined and accessible, has the capacity for adaptive change, and clearly contains the responsible substrates. This study was an attempt to determine whether the spinal stretch reflex (SSR), the initial, purely spinal, portion of the muscle stretch response, which satisfies the first requirement, also satisfies the second, capacity for adaptive change. Monkeys prepared with chronic fine-wire biceps electromyographic (EMG) electrodes were trained to maintain elbow position and a given level of biceps background EMG activity against constant extension torque. At random times, a brief additional extension torque pulse extended the elbow and elicited the biceps SSR. Under the control mode, reward always followed. Under the SSR increases or SSR decreases mode, reward followed only if the absolute value of biceps EMG from 14 to 24 ms after stretch onset (the SSR interval) was above or below a set value. Animals performed 3,000-6,000 trials/day over data-collection periods of up to 15 mo. Background EMG and the initial 30 ms of pulse-induced extension remained stable throughout data collection. Under the SSR increases or SSR decreases mode, SSR amplitude (EMG amplitude in the SSR interval minus background EMG amplitude) changed appropriately. Change was evident in 5-10 days and progressed over at least 4 wk. The SSR increased (SSR increases) to 140-190% control amplitude or decreased (SSR decreases) to 22-79%. SSR change did not regress over 12-day gaps in task performance. A second pair of biceps electrodes, monitored simultaneously, supplied comparable data, indicating that SSR amplitude change occurred throughout the muscle. Beyond 40 ms after pulse onset, elbow extension was inversely correlated with SSR amplitude. The delay between the SSR and its apparent effect on movement is consistent with expected motor-unit contraction time. The data demonstrate that the SSR is capable of adaptive change. At present the most likely site(s) of the mechanism of SSR amplitude change are the Ia synapse and/or the muscle spindle. Available related evidence suggests persistent segmental change may in fact come to mediate SSR amplitude change. If so, such segmental change would constitute a technically accessible fragment of a memory.10aSpinal Cord1 aWolpaw, Jonathan1 aBraitman, D., J.1 aSeegal, R., F.  uhttp://www.ncbi.nlm.nih.gov/pubmed/666332701262nas a2200241   4500008004100000022001400041245007900055210006900134260001200203300001400215490000800229520055700237653001600794653002200810653002300832653001500855653001300870653003000883653001600913100002300929700002100952856004700973       1982                        eng d  a0006-899300aDopamine receptor-mediated depression of spinal monosynaptic transmission.0 aDopamine receptormediated depression of spinal monosynaptic tran  c06/1982  a247–2540 v2423 aThe effects of the dopamine agonists apomorphine, lisuride and lergotrile were evaluated on cat spinal cord monosynaptic transmission by stimulating the dorsal root and recording the ventral root compound action potential. All 3 agonists decreased the area of the monosynaptic response. This effect was prevented by pretreatment with the dopamine antagonists haloperidol and metoclopramide, but not with the alpha-adrenergic antagonist phentolamine. These results suggest the existence of spinal cord dopamine receptors which can modulate motor output.10aapomorphine10adopamine agonists10adopamine receptors10alergotrile10alisuride10amonosynaptic transmission10aSpinal Cord1 aCarp, Jonathan, S.1 aAnderson, R., J.  uhttp://www.ncbi.nlm.nih.gov/pubmed/6126249