02456nas a2200157   4500008004100000022001400041245011700055210006900172260000800241520191100249100002502160700002102185700002102206700002302227856004802250       2017                        eng d  a1557-904200aSpinal transection alters external urethral sphincter activity during spontaneous voiding in freely-moving rats.0 aSpinal transection alters external urethral sphincter activity d  cMay3 aThe rat is a commonly used model for the study of lower urinary tract function before and after spinal cord injury. We have previously reported that in unanesthetized, freely-moving rats, although phasic external urethral sphincter (EUS) activity (bursting) is most common during micturition, productive voiding can occur in the absence of bursting, which differs from results seen in anesthetized or unanesthetized restrained animals. The purpose of the present study was to characterize EUS behavior in unanesthetized, freely-moving rats before and after mid-thoracic (T8) or thoraco-lumbar (T13-L1) spinal transection to determine how EUS behavior after spinal cord injury differs from that seen in anesthetized or unanesthetized restrained rats. Several abnormalities became evident that were comparable after transection at either level including: repetitive non-voiding EUS contractions; increased prevalence, intensity and duration of EUS bursting; decreased rate of urine evacuation during bursting; increased void size and decreased number of daily voids; shorter inter-burst silent period and increased frequency of bursting; and loss of the direct linear relationships that are evident in intact animals between void size and bursting silent period. These data suggest that transection-induced delayed initiation of EUS bursting allows co-contraction of the bladder and the EUS that prevents or limits urine evacuation, resulting in a detrusor-sphincter dyssynergia-like phenomenon. In addition, the higher-than-normal frequency at which EUS bursting occurs after transection is associated with shorter silent periods during which urine typically flows, which interferes with voiding by slowing the rate of urine evacuation. That results were comparable after either transection suggests that the central pattern generator responsible for EUS bursting is located caudal to the L1 spinal segment.1 aLaPallo, Brandon, K.1 aWolpaw, Jonathan1 aChen, Xiang Yang1 aCarp, Jonathan, S.  uhttp://www.ncbi.nlm.nih.gov/pubmed/2846773601079nas a2200181   4500008004100000022001400041245011000055210006900165260000800234300001400242490000700256520049600263100002500759700002100784700002100805700002300826856004800849       2016                        eng d  a1520-677700aContribution of the external urethral sphincter to urinary void size in unanesthetized unrestrained rats.0 aContribution of the external urethral sphincter to urinary void   cAug  a696–7020 v353 aIn anesthetized rats, voiding is typically associated with phasic activation (bursting) of the external urethral sphincter (EUS). During spontaneous voiding in unanesthetized, unrestrained rats, EUS bursting is the most common form of EUS activity exhibited, but it is not necessary for productive voiding to occur. The aim of the present study was to determine which aspects of EUS activity contributed to void size during bursting and non-bursting voiding in conscious, freely moving rats.1 aLaPallo, Brandon, K.1 aWolpaw, Jonathan1 aChen, Xiang Yang1 aCarp, Jonathan, S.  uhttp://www.ncbi.nlm.nih.gov/pubmed/2599507402577nas a2200301   4500008004100000022001400041245010600055210006900161260001200230300001200242490000800254520171500262653001201977653002601989653002102015653001102036653001502047653000902062653002502071653001202096653001402108653001602122100002402138700002102162700002102183700002302204856004802227       2014                        eng d  a1522-146600aLong-term recording of external urethral sphincter EMG activity in unanesthetized, unrestrained rats.0 aLongterm recording of external urethral sphincter EMG activity i  c08/2014  aF485-970 v3073 a<p>The external urethral sphincter muscle (EUS) plays an important role in urinary function and often contributes to urinary dysfunction. EUS study would benefit from methodology for longitudinal recording of electromyographic activity (EMG) in unanesthetized animals, but this muscle is a poor substrate for chronic intramuscular electrodes, and thus the required methodology has not been available. We describe a method for long-term recording of EUS EMG by implantation of fine wires adjacent to the EUS that are secured to the pubic bone. Wires pass subcutaneously to a skull-mounted plug and connect to the recording apparatus by a flexible cable attached to a commutator. A force transducer-mounted cup under a metabolic cage collected urine, allowing recording of EUS EMG and voided urine weight without anesthesia or restraint. Implant durability permitted EUS EMG recording during repeated (up to 3 times weekly) 24-h sessions for more than 8 wk. EMG and voiding properties were stable over weeks 2-8. The degree of EUS phasic activity (bursting) during voiding was highly variable, with an average of 25% of voids not exhibiting bursting. Electrode implantation adjacent to the EUS yielded stable EMG recordings over extended periods and eliminated the confounding effects of anesthesia, physical restraint, and the potential for dislodgment of the chronically implanted intramuscular electrodes. These results show that micturition in unanesthetized, unrestrained rats is usually, but not always, associated with EUS bursting. This methodology is applicable to studying EUS behavior during progression of gradually evolving disease and injury models and in response to therapeutic interventions.</p>10aAnimals10aElectrodes, Implanted10aElectromyography10aFemale10aPubic Bone10aRats10aRats, Sprague-Dawley10aUrethra10aUrination10aUrodynamics1 aLaPallo, Brandon, K1 aWolpaw, Jonathan1 aChen, Xiang Yang1 aCarp, Jonathan, S.  uhttp://www.ncbi.nlm.nih.gov/pubmed/2499089502531nas a2200205   4500008004100000022001400041245009300055210006900148260001200217300001600229490000800245520189500253653001202148100002302160700002302183700002902206700002102235700002102256856004802277       2010                        eng d  a1522-159800aExternal urethral sphincter motoneuron properties in adult female rats studied in vitro.0 aExternal urethral sphincter motoneuron properties in adult femal  c09/2010  a1286–13000 v1043 aThe external urethral sphincter (EUS) muscle plays a crucial role in lower urinary tract function: its activation helps maintain continence, whereas its relaxation contributes to micturition. To determine how the intrinsic properties of its motoneurons contribute to its physiological function, we have obtained intracellular current-clamp recordings from 49 EUS motoneurons in acutely isolated spinal cord slices from adult female rats. In all, 45% of EUS motoneurons fired spontaneously and steadily (average rate = 12-27 pulses/s). EUS motoneurons were highly excitable, having lower rheobase, higher input resistance, and smaller threshold depolarization than those of rat hindlimb motoneurons recorded in vitro. Correlations between these properties and afterhyperpolarization half-decay time are consistent with EUS motoneurons having characteristics of both fast and slow motor unit types. EUS motoneurons with a slow-like spectrum of properties exhibited spontaneous firing more often than those with fast-like characteristics. During triangular current ramp-induced repetitive firing, recruitment typically occurred at lower current levels than those at derecruitment, although the opposite pattern occurred in 10% of EUS motoneurons. This percentage was likely underestimated due to firing rate adaptation. These findings are consistent with the presence of a basal level of persistent inward current (PIC) in at least some EUS motoneurons. The low EUS motoneuron current and voltage thresholds make them readily recruitable, rendering them well suited to their physiological role in continence. The expression of firing behaviors consistent with PIC activation in this highly reduced preparation raises the possibility that in the intact animal, PICs contribute to urinary function not only through neuromodulator-dependent but also through neuromodulator-independent mechanisms.10aUrethra1 aCarp, Jonathan, S.1 aTennissen, Ann, M.1 aLiebschutz, Jennifer, E.1 aChen, Xiang Yang1 aWolpaw, Jonathan  uhttp://www.ncbi.nlm.nih.gov/pubmed/2057397601519nas a2200301   4500008004100000022001400041245009500055210006900150260001200219300001400231490001700245520064100262653001300903653002400916653001500940653001500955653002400970653001900994653002301013100002101036700001301057700001301070700001901083700002301102700002301125700002101148856004801169       2010                        eng d  a1749-663200aReflex conditioning: a new strategy for improving motor function after spinal cord injury.0 aReflex conditioning a new strategy for improving motor function   c06/2010  aE12–E210 v1198 Suppl 13 aSpinal reflex conditioning changes reflex size, induces spinal cord plasticity, and modifies locomotion. Appropriate reflex conditioning can improve walking in rats after spinal cord injury (SCI). Reflex conditioning offers a new therapeutic strategy for restoring function in people with SCI. This approach can address the specific deficits of individuals with SCI by targeting specific reflex pathways for increased or decreased responsiveness. In addition, once clinically significant regeneration can be achieved, reflex conditioning could provide a means of reeducating the newly (and probably imperfectly) reconnected spinal cord.10aH-Reflex10alearning and memory10aLocomotion10aplasticity10areflex conditioning10aRehabilitation10aspinal cord injury1 aChen, Xiang Yang1 aChen, Yi1 aWang, Yu1 aThompson, Aiko1 aCarp, Jonathan, S.1 aSegal, Richard, L.1 aWolpaw, Jonathan  uhttp://www.ncbi.nlm.nih.gov/pubmed/2059053402323nas a2200217   4500008004100000022001400041245007800055210006900133260001200202300001400214490000800228520164900236653003201885100002301917700002301940700002501963700002701988700002102015700002102036856004802057       2008                        eng d  a0022-307700aAn in vitro protocol for recording from spinal motoneurons of adult rats.0 ain vitro protocol for recording from spinal motoneurons of adult  c07/2008  a474–4810 v1003 aIn vitro slice preparations of CNS tissue are invaluable for studying neuronal function. However, up to now, slice protocols for adult mammal spinal motoneurons–the final common pathway for motor behaviors–have been available for only limited portions of the spinal cord. In most cases, these preparations have not been productive due to the poor viability of motoneurons in vitro. This report describes and validates a new slice protocol that for the first time provides reliable intracellular recordings from lumbar motoneurons of adult rats. The key features of this protocol are: preexposure to 100% oxygen; laminectomy prior to perfusion; anesthesia with ketamine/xylazine; embedding the spinal cord in agar prior to slicing; and, most important, brief incubation of spinal cord slices in a 30% solution of polyethylene glycol to promote resealing of the many motoneuron dendrites cut during sectioning. Together, these new features produce successful recordings in 76% of the experiments and an average action potential amplitude of 76 mV. Motoneuron properties measured in this new slice preparation (i.e., voltage and current thresholds for action potential initiation, input resistance, afterhyperpolarization size and duration, and onset and offset firing rates during current ramps) are comparable to those recorded in vivo. Given the mechanical stability and precise control over the extracellular environment afforded by an in vitro preparation, this new protocol can greatly facilitate electrophysiological and pharmacological study of these uniquely important neurons and other delicate neuronal populations in adult mammals.10aTissue and Organ Harvesting1 aCarp, Jonathan, S.1 aTennissen, Ann, M.1 aMongeluzi, Donna, L.1 aDudek, Christopher, J.1 aChen, Xiang Yang1 aWolpaw, Jonathan  uhttp://www.ncbi.nlm.nih.gov/pubmed/1846317702087nas a2200205   4500008004100000022001400041245010700055210006900162260001200231300001600243490000700259520144800266653001701714100002401731700001301755700002301768700002101791700002101812856004801833       2007                        eng d  a0022-307700aRecovery of electromyographic activity after transection and surgical repair of the rat sciatic nerve.0 aRecovery of electromyographic activity after transection and sur  c02/2007  a1127–11340 v973 aThe recovery of soleus (SOL), gastrocnemius (GAS), and tibialis anterior (TA) electromyographic activity (EMG) after transection and surgical repair of the sciatic nerve was studied in Sprague-Dawley rats using chronically implanted stimulation and recording electrodes. Spontaneous EMG activity in SOL and GAS and direct muscle (M) responses to posterior tibial nerve stimulation persisted for < or =2 days after sciatic nerve transection, but SOL and GAS H-reflexes disappeared immediately. Spontaneous EMG activity began to return 2-3 wk after transection, rose nearly to pretransection levels by 60 days, and persisted for the duration of the study period (120 days). Recovery of stimulus-evoked EMG responses began about 30 days after sciatic nerve transection as multiple small responses with a wide range of latencies. Over time, the latencies of these fractionated responses shortened, their amplitudes increased, and they merged into a distinct short-latency component (the putative M response) and a distinct long-latency component (the putative H-reflex). The extent of recovery of stimulation-evoked EMG was modest: even 100 days after sciatic nerve transection, the responses were still much smaller than those before transection. Similar gradual development of responses to posterior tibial nerve stimulation was also seen in TA, suggesting that some regenerating fibers sent branches into both tibial and common peroneal nerves.10aTibial Nerve1 aEnglish, Arthur, W.1 aChen, Yi1 aCarp, Jonathan, S.1 aWolpaw, Jonathan1 aChen, Xiang Yang  uhttp://www.ncbi.nlm.nih.gov/pubmed/1712231002084nas a2200229   4500008004100000022001400041245009200055210006900147260001200216300001400228490000700242520141400249653001701663100002101680700002201701700001301723700001301736700001301749700002301762700002101785856004801806       2007                        eng d  a0022-307700aSpinal and supraspinal effects of long-term stimulation of sensorimotor cortex in rats.0 aSpinal and supraspinal effects of longterm stimulation of sensor  c08/2007  a878–8870 v983 aSensorimotor cortex (SMC) modifies spinal cord reflex function throughout life and is essential for operant conditioning of the H-reflex. To further explore this long-term SMC influence over spinal cord function and its possible clinical uses, we assessed the effect of long-term SMC stimulation on the soleus H-reflex. In freely moving rats, the soleus H-reflex was measured 24 h/day for 12 wk. The soleus background EMG and M response associated with H-reflex elicitation were kept stable throughout. SMC stimulation was delivered in a 20-day-on/20-day-off/20-day-on protocol in which a train of biphasic 1-ms pulses at 25 Hz for 1 s was delivered every 10 s for the on-days. The SMC stimulus was automatically adjusted to maintain a constant descending volley. H-reflex size gradually increased during the 20 on-days, stayed high during the 20 off-days, and rose further during the next 20 on-days. In addition, the SMC stimulus needed to maintain a stable descending volley rose steadily over days. It fell during the 20 off-days and rose again when stimulation resumed. These results suggest that SMC stimulation, like H-reflex operant conditioning, induces activity-dependent plasticity in both the brain and the spinal cord and that the plasticity responsible for the H-reflex increase persists longer after the end of SMC stimulation than that underlying the change in the SMC response to stimulation.10aTime Factors1 aChen, Xiang Yang1 aPillai, Shreejith1 aChen, Yi1 aWang, Yu1 aChen, Lu1 aCarp, Jonathan, S.1 aWolpaw, Jonathan  uhttp://www.ncbi.nlm.nih.gov/pubmed/1752217902091nas 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/1615178102319nas 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/1683765902728nas 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/1664718102294nas a2200193   4500008004100000022001400041245013100055210006900186260001200255300001400267490000700281520166100288653002501949100002101974700002301995700001302018700002102031856004802052       2006                        eng d  a0022-307700aSensorimotor cortex ablation prevents H-reflex up-conditioning and causes a paradoxical response to down-conditioning in rats.0 aSensorimotor cortex ablation prevents Hreflex upconditioning and  c07/2006  a119–1270 v963 aOperant conditioning of the H-reflex, a simple model for skill acquisition, requires the corticospinal tract (CST) and does not require other major descending pathways. To further explore its mechanisms, we assessed the effects of ablating contralateral sensorimotor cortex (cSMC). In 22 Sprague-Dawley rats, the hindlimb area of left cSMC was ablated. EMG electrodes were implanted in the right soleus muscle and a stimulating cuff was placed around the right posterior tibial nerve. When EMG remained in a specified range, nerve stimulation just above the M response threshold elicited the H-reflex. In control mode, no reward occurred. In conditioning mode, reward occurred if H-reflex size was above (HRup mode) or below (HRdown mode) a criterion value. After exposure to the control mode for > or = 10 days, each rat was exposed for another 50 days to the control mode, the HRup mode, or the HRdown mode. In control and HRup rats, final H-reflex size was not significantly different from initial H-reflex size. In contrast, in HRdown rats, final H-reflex size was significantly increased to an average of 136% of initial size. Thus like recent CST transection, cSMC ablation greatly impaired up-conditioning. However, unlike recent CST transection, cSMC produced a paradoxical response to down-conditioning: the H-reflex actually increased. These results confirm the critical role of cSMC in H-reflex conditioning and suggest that this role extends beyond producing essential CST activity. Its interactions with ipsilateral SMC or other areas contribute to the complex pattern of spinal and supraspinal plasticity that underlies H-reflex conditioning.10aSomatosensory Cortex1 aChen, Xiang Yang1 aCarp, Jonathan, S.1 aChen, Lu1 aWolpaw, Jonathan  uhttp://www.ncbi.nlm.nih.gov/pubmed/1659806202315nas 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/1602684801648nas a2200229   4500008004100000022001400041245010000055210006900155260001200224300001400236490000800250520093900258653002101197653002401218653002701242653002001269653001401289100002301303700002301326700002101349856004801370       2003                        eng d  a0014-481900aConduction velocity is inversely related to action potential threshold in rat motoneuron axons.0 aConduction velocity is inversely related to action potential thr  c06/2003  a497–5050 v1503 aIntra-axonal recordings were performed in ventral roots of rats in vitro to study the conduction velocity and firing threshold properties of motoneuron axons. Mean values +/- SD were 30.5+/-5.6 m/s for conduction velocity and 11.6+/-4.5 mV for the depolarization from the resting potential required to reach firing threshold (threshold depolarization). Conduction velocity varied inversely and significantly with threshold depolarization ( P=0.0002 by linear regression). This relationship was evident even after accounting for variation in conduction velocity associated with action potential amplitude, injected current amplitude, or body weight. Conduction velocity also varied inversely with the time to action potential onset during just-threshold current pulse injection. These data suggest that the time course of depolarization leading to action potential initiation contributes to the speed of conduction in motoneuron axons.10aaction potential10aconduction velocity10aintra-axonal recording10amyelinated axon10athreshold1 aCarp, Jonathan, S.1 aTennissen, Ann, M.1 aWolpaw, Jonathan  uhttp://www.ncbi.nlm.nih.gov/pubmed/1271511802878nas a2200241   4500008004100000022001400041245009400055210006900149260001200218300001200230490000800242520217200250653001802422653001902440653001302459653001502472653002302487100002102510700002302531700001302554700002102567856004802588       2002                        eng d  a0014-481900aCorticospinal tract transection prevents operantly conditioned H-reflex increase in rats.0 aCorticospinal tract transection prevents operantly conditioned H  c05/2002  a88–940 v1443 aOperant conditioning of the H-reflex, the electrical analog 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 (i.e., up-condition) or decrease (i.e., down-condition) the soleus H-reflex. Earlier work showed that corticospinal tract transection prevents acquisition and maintenance of H-reflex down-conditioning while transection of other major spinal cord tracts does not. This study explores the effects on acquisition of up-conditioning of the right soleus H-reflex of mid-thoracic transection of: the right lateral column (LC, five rats) (containing the rubrospinal, vestibulospinal, and reticulospinal tracts); the entire dorsal column (DC, six rats) [containing the main corticospinal tract (CST) and the dorsal ascending tract (DA)]; the CST alone (five rats); or the DA alone (seven rats). After initial (i.e., control) H-reflex amplitude was determined, the rat was exposed for 50 days to the up-conditioning mode in which reward was given when the H-reflex was above a criterion value. H-reflex amplitude at the end of up-conditioning was compared to initial H-reflex amplitude. An increase > or =20% was defined as successful up-conditioning. In intact rats, H-reflex amplitude at the end of up-conditioning averaged 164% (+/-10%, SE), and 81% were successful. In the present study, LC and DA rats were similar to intact rats in final H-reflex amplitude and percent successful. In contrast, results for DC and CST rats were significantly different from those of intact rats. In the six DC rats, final H-reflex amplitude averaged 105% (+/-3)% of control and none was successful; and in the five CST rats, final H-reflex amplitude averaged 94% (+/-3)% and none was successful. The results indicate that the main CST, located in the dorsal column, is essential for H-reflex up-conditioning as it is for down-conditioning, while the dorsal column ascending tract and the ipsilateral lateral column (containing the main rubrospinal, vestibulospinal, and reticulospinal tracts) do not appear to be essential.10adorsal column10alateral column10aLearning10aplasticity10aspinal cord injury1 aChen, Xiang Yang1 aCarp, Jonathan, S.1 aChen, Lu1 aWolpaw, Jonathan  uhttp://www.ncbi.nlm.nih.gov/pubmed/1197676201697nas a2200229   4500008004100000022001400041245009400055210006900149260001200218300001400230490000700244520103100251653001401282653002501296653001501321653001001336100001301346700002301359700002201382700001501404856004801419       2002                        eng d  a0024-320500aCorticospinal transmission to motoneurons in cervical spinal cord slices from adult rats.0 aCorticospinal transmission to motoneurons in cervical spinal cor  c12/2002  a389–3960 v723 aCervical spinal cord slices were prepared from adult rats. Intracellular recordings from motoneurons revealed that electrical stimulation of the ventralmost part of the dorsal funiculus (which contains primarily descending corticospinal axons) elicited EPSPs in 75% of the neurons. The latencies of these EPSPs tended to be shorter than those elicited by dorsal horn gray matter stimulation. Pairs of subthreshold dorsal funiculus stimuli were able to elicit action potentials in motoneurons. These data are consistent with previous morphological and electrophysiological studies indicating that cervical motoneurons receive both mono-and polysynaptic corticospinal inputs. In addition, motoneurons were markedly depolarized by iontophoretic application of AMPA or KA (7 out of 7 neurons), but only weakly depolarized by NMDA (1 out of 6 neurons). CNQX (but not AP-5) blocked EPSPs elicited by dorsal funiculus stimulation. Thus, corticospinal transmission to motoneurons is mediated primarily by non-NMDA glutamate receptors.10aadult rat10acervical spinal cord10amotoneuron10aslice1 aHori, N.1 aCarp, Jonathan, S.1 aCarpenter, D., O.1 aAkaike, N.  uhttp://www.ncbi.nlm.nih.gov/pubmed/1246787902917nas a2200265   4500008004100000022001400041245009700055210006900152260001200221300001000233490000800243520213200251653002202383653001202405653002102417653001302438653001802451653002102469653000902490653004102499100001902540700002302559700002102582856004802603       2002                        eng d  a0165-027000aTemporal transformation of multiunit activity improves identification of single motor units.0 aTemporal transformation of multiunit activity improves identific  c02/2002  a87-980 v1143 a<p><span style="font-family: arial, helvetica, clean, sans-serif; font-size: 13px; line-height: 17px;">This report describes a temporally based method for identifying repetitive firing of motor units. This&nbsp;</span><span class="highlight" style="font-family: arial, helvetica, clean, sans-serif; font-size: 13px; line-height: 17px;">approach</span><span style="font-family: arial, helvetica, clean, sans-serif; font-size: 13px; line-height: 17px;">&nbsp;is ideally suited to spike trains with negative serially correlated inter-spike intervals (ISIs). It can also be applied to spike trains in which ISIs exhibit little serial correlation if their coefficient of variation (COV) is sufficiently low. Using a novel application of the Hough transform, this method (i.e. the modified Hough transform (MHT)) maps motor unit action potential (MUAP) firing times into a feature space with ISI and offset (defined as the latency from an arbitrary starting time to the first MUAP in the train) as dimensions. Each MUAP firing time corresponds to a pattern in the feature space that represents all possible MUAP trains with a firing at that time. Trains with stable ISIs produce clusters in the feature space, whereas randomly firing trains do not. The MHT provides a direct estimate of mean firing rate and its variability for the entire data segment, even if several individual MUAPs are obscured by firings from other motor units. Addition of this method to a shape-based classification&nbsp;</span><span class="highlight" style="font-family: arial, helvetica, clean, sans-serif; font-size: 13px; line-height: 17px;">approach</span><span style="font-family: arial, helvetica, clean, sans-serif; font-size: 13px; line-height: 17px;">&nbsp;markedly improved rejection of false positives using simulated data and identified spike trains in whole muscle electromyographic recordings from rats. The relative independence of the MHT from the need to correctly classify individual firings permits a global description of stable repetitive firing behavior that is complementary to shape-based approaches to MUAP classification.</span></p>10aAction Potentials10aAnimals10aElectromyography10aH-Reflex10aMotor Neurons10aMuscle, Skeletal10aRats10aSignal Processing, Computer-Assisted1 aSchalk, Gerwin1 aCarp, Jonathan, S.1 aWolpaw, Jonathan  uhttp://www.ncbi.nlm.nih.gov/pubmed/1185004301678nas a2200277   4500008004100000022001400041245009700055210006900152260001200221300001000233490000800243520088300251653002201134653002101156653001301177653002501190653001601215653001501231653001801246653000801264100002301272700002101295700001501316700002101331856004801352       2001                        eng d  a0304-394000aEffects of chronic nerve cuff and intramuscular electrodes on rat triceps surae motor units.0 aEffects of chronic nerve cuff and intramuscular electrodes on ra  c10/2001  a1–40 v3123 aIn order to assess the long-term effects of implanted electrodes on motor unit properties, we studied triceps surae (TS) motor units in rats implanted for 3-10 months with a tibial nerve cuff electrode for H-reflex elicitation and intramuscular electrodes for recording TS electromyographic activity. Motor units with sag from implanted rats displayed greater tetanic force than those from unimplanted rats. Motor units without sag had shorter twitch contraction times. This disrupted the relationship between sag and contraction time that was always present in unimplanted rats. These differences were consistent with a small degree of muscle denervation and subsequent reinnervation. Further analyses ascribed this effect to the nerve cuff rather than to the intramuscular electrodes. Comparable changes in motor unit properties may occur in humans with implanted nerve cuffs.10achronic recording10acontraction time10aH-Reflex10aimplanted electrodes10amotor units10anerve cuff10areinnervation10asag1 aCarp, Jonathan, S.1 aChen, Xiang Yang1 aSheikh, H.1 aWolpaw, Jonathan  uhttp://www.ncbi.nlm.nih.gov/pubmed/1157883102272nas a2200241   4500008004100000022001400041245007000055210006800125260001200193300001400205490000800219520158400227653001301811653002001824653002501844653001501869653001801884100002301902700002101925700001501946700002101961856004801982       2001                        eng d  a0014-481900aMotor unit properties after operant conditioning of rat H-reflex.0 aMotor unit properties after operant conditioning of rat Hreflex  c10/2001  a382–3860 v1403 aOperant conditioning of the H-reflex produces plasticity at several sites in the spinal cord, including the motoneuron. This study assessed whether this spinal cord plasticity is accompanied by changes in motor unit contractile properties. Thirty-one adult male Sprague-Dawley rats implanted for chronic recording of triceps surae electromyographic activity and H-reflex elicitation were exposed for at least 40 days to HRup or HRdown training, in which reward occurred when the H-reflex was greater than (12 HRup rats) or less than (12 HRdown rats) a criterion value, or continued under the control mode in which the H-reflex was simply measured (7 HRcon rats). At the end of H-reflex data collection, rats were anesthetized and the contractile properties of 797 single triceps surae motor units activated by intraaxonal (or intramyelin) current injection were determined. Motor units were classified as S, FR, Fint, or FF on the basis of sag and fatigue properties. Maximum tetanic force and twitch contraction time were also measured. HRdown rats exhibited a significant increase in the fatigue index of fast-twitch motor units. This resulted in a significant decrease in the percentage of Fint motor units and a significant increase in that of FR motor units. HRup conditioning had no effect on fatigue index. Neither HRup nor HRdown conditioning affected maximum tetanic force or twitch contraction time. These data are consistent with the hypothesis that conditioning mode-specific change in motoneuron firing patterns causes activity-dependent change in muscle properties.10aH-Reflex10amotor unit type10aoperant conditioning10aplasticity10atriceps surae1 aCarp, Jonathan, S.1 aChen, Xiang Yang1 aSheikh, H.1 aWolpaw, Jonathan  uhttp://www.ncbi.nlm.nih.gov/pubmed/1168131402242nas 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/1120629003180nas a2200193   4500008004100000022001400041245007800055210006900133260001200202300001600214490000700230520258700237653002402824100002302848700002502871700002102896700002102917856004802938       1999                        eng d  a0022-307700aSag during unfused tetanic contractions in rat triceps surae motor units.0 aSag during unfused tetanic contractions in rat triceps surae mot  c06/1999  a2647–26610 v813 aContractile properties and conduction velocity were studied in 202 single motor units of intact rat triceps surae muscles activated by intra-axonal (or intra-myelin) current injection in L5 or L6 ventral root to assess the factors that determine the expression of sag (i.e., decline in force after initial increase during unfused tetanic stimulation). Sag was consistently detected in motor units with unpotentiated twitch contraction times <20 ms. However, the range of frequencies at which sag was expressed varied among motor units such that there was no single interstimulus interval (ISI), with or without adjusting for twitch contraction time, at which sag could be detected reliably. Further analysis indicated that using the absence of sag as a criterion for identifying slow-twitch motor units requires testing with tetani at several different ISIs. In motor units with sag, the shape of the force profile varied with tetanic frequency and contractile properties. Simple sag force profiles (single maximum reached late in the tetanus followed by monotonic decay) tended to occur at shorter ISIs and were observed more frequently in fatigue-resistant motor units with long half-relaxation times and small twitch amplitudes. Complex sag profiles reached an initial maximum early in the tetanus, tended to occur at longer ISIs, and were more common in fatigue-sensitive motor units with long half-relaxation times and large twitch amplitudes. The differences in frequency dependence and force maximum location suggested that these phenomena represented discrete entities. Successive stimuli elicited near-linear increments in force during tetani in motor units that never exhibited sag. In motor units with at least one tetanus displaying sag, tetanic stimulation elicited large initial force increments followed by rapidly decreasing force increments. That the latter force envelope pattern occurred in these units even in tetani without sag suggested that the factors responsible for sag were expressed in the absence of overt sag. The time-to-peak force (TTP) of the individual contractions during a tetanus decreased in tetani with sag. Differences in the pattern of TTP change during a tetanus were consistent with the differences in force maximum location between tetani exhibiting simple and complex sag. Tetani from motor units that never exhibited sag did not display a net decrease in TTP during successive contractions. These data were consistent with the initial force decrement of sag resulting from a transient reduction in the duration of the contractile state.10aRegression Analysis1 aCarp, Jonathan, S.1 aHerchenroder, P., A.1 aChen, Xiang Yang1 aWolpaw, Jonathan  uhttp://www.ncbi.nlm.nih.gov/pubmed/1036838502073nas a2200169   4500008004100000022001400041245008400055210006900139260001200208300001600220490000700236520155800243653001101801100002301812700002101835856004701856       1995                        eng d  a0022-307700aMotoneuron properties after operantly conditioned increase in primate H-reflex.0 aMotoneuron properties after operantly conditioned increase in pr  c04/1995  a1365–13730 v733 a1. Monkeys can increase (HRup conditioning mode) or decrease (HRdown conditioning mode) the triceps surae (TS) H-reflex in response to an operant conditioning task. This conditioning modifies the spinal cord. To define this spinal cord plasticity and its role in the behavioral change (H-reflex increase or decrease), we have recorded intracellularly from TS motoneurons in conditioned animals. The present report describes data from HRup animals and compares them with data from previously studied naive (NV; i.e., unconditioned) animals. 2. Thirteen monkeys (Macaca nemestrina, male, 3.8-7.1 kg) were exposed to the HRup conditioning mode, in which reward occurred when H-reflex size in one leg (i.e., the trained leg) was above a criterion value. Conditioning was successful (i.e., increase of > or = 20%) in 12 of the 13 animals. At the end of conditioning, H-reflex size in the trained leg averaged 188% of its initial value, whereas size in the control leg averaged 134% of its initial value. 3. Intracellular recordings were obtained from 136 TS motoneurons on trained (UT + motoneurons) and control (UC + motoneurons) sides of the successful animals. Measurements included axonal conduction velocity, input resistance, time constant, electrotonic length, rheobase, firing threshold to current injection, afterhyperpolarization duration and amplitude, and composite homonymous and heteronymous excitatory postsynaptic potential (EPSP) size and shape. Results were compared with intracellular data from NV animals.(ABSTRACT TRUNCATED AT 250 WORDS)10aReward1 aCarp, Jonathan, S.1 aWolpaw, Jonathan  uhttp://www.ncbi.nlm.nih.gov/pubmed/754394201900nas a2200181   4500008004100000022001400041245008300055210006900138260001200207300001400219490000700233520134800240653002001588100001901608700002301627700002101650856004701671       1995                        eng d  a0022-307700aOperantly conditioned motoneuron plasticity: possible role of sodium channels.0 aOperantly conditioned motoneuron plasticity possible role of sod  c02/1995  a867–8710 v733 a1. Learning is traditionally thought to depend on synaptic plasticity. However, recent work shows that operantly conditioned decrease in the primate H reflex is associated with an increase in the depolarization needed to fire the spinal motoneuron (VDEP) and a decrease in its conduction velocity (CV). Furthermore, the increase in VDEP appears to be largely responsible for the H-reflex decrease. The conjunction of these changes in VDEP and CV suggests that an alteration in Na+ channel properties throughout the soma and axon could be responsible. 2. A mathematical model of the mammalian myelinated axon was used to test whether a positive shift in the voltage dependence of Na+ channel activation, a decrease in Na+ channel peak permeability, or changes in other fiber properties could have accounted for the experimental findings. 3. A positive shift of 2.2 mV in Na+ channel activation reproduced the experimentally observed changes in VDEP and CV, whereas a reduction in Na+ channel permeability or changes in other fiber properties did not. 4. These results are consistent with the hypothesis that operantly conditioned decrease in the primate H reflex is largely due to a positive shift in the voltage dependence of Na+ channel activation. Recent studies suggest that change in activation of protein kinase C may mediate this effect.10aSodium Channels1 aHalter, J., A.1 aCarp, Jonathan, S.1 aWolpaw, Jonathan  uhttp://www.ncbi.nlm.nih.gov/pubmed/776014103057nas a2200169   4500008004100000022001400041245008900055210006900144260001200213300001400225490000700239520252400246653002602770100002302796700002102819856004702840       1994                        eng d  a0022-307700aMotoneuron plasticity underlying operantly conditioned decrease in primate H-reflex.0 aMotoneuron plasticity underlying operantly conditioned decrease   c07/1994  a431–4420 v723 a1. Monkeys can gradually increase or decrease the size of the triceps surae H-reflex in response to an operant conditioning task. This conditioning modifies the spinal cord. To determine the location and nature of the spinal cord plasticity and define its role in the behavioral change (i.e., H-reflex increase or decrease) we have recorded intracellularly from triceps surae motoneurons in conditioned animals and compared the results with data from naive (i.e., unconditioned) animals. 2. Eleven monkeys (Macaca nemestrina, male) were exposed to the HRdown conditioning mode, in which reward occurred when H-reflex size in one leg (i.e., the trained leg) was below a criterion value. In six animals (5.1-8.2 kg) H-reflex size in the trained leg fell to 24-58% of its initial value, whereas in the other five animals (4.0-5.5 kg) it remained at 92-114% of its initial value. This outcome, which was in accord with recent data indicating that success in HRdown conditioning is age dependent, allowed comparison of intracellular data from successful HRdown animals with data from unsuccessful animals as well as with data from naive (i.e., unconditioned) animals. 3. Intracellular recordings were obtained from 221 triceps surae motoneurons on trained and control sides of successful and unsuccessful HRdown animals. Measurements included axonal conduction velocity, input resistance, time constant, electrotonic length, rheobase, firing threshold, afterhyperpolarization duration and amplitude, and composite homonymous and heteronymous excitatory postsynaptic potentials to peripheral nerve stimulation. Results were compared with data from 109 triceps surae motoneurons in naive animals. 4. Motoneurons from the trained side of successful HRdown animals had a significantly more positive average firing threshold (-52 vs. -55 mV) and a significantly lower average conduction velocity (67 vs. 71 m/s) than those from naive animals. In contrast, motoneurons from the trained side of unsuccessful HRdown animals were not significantly different from naive motoneurons. 5. These data are consistent with the hypothesis that operantly conditioned decrease in H-reflex size is due to a positive shift in motoneuron firing threshold and a consequent increase in the depolarization needed to reach that threshold. 6. The more positive firing threshold, if present in the axon as well as in the soma, could also account for the decreased conduction velocity observed in motoneurons from the trained side of successful animals.10aSynaptic Transmission1 aCarp, Jonathan, S.1 aWolpaw, Jonathan  uhttp://www.ncbi.nlm.nih.gov/pubmed/796502502420nas a2200181   4500008004100000022001400041245009700055210006900152260000900221300001400230490000800244520186300252653001202115100002202127700002302149700001902172856004702191       1994                        eng d  a0065-259800aTransmitter and electrical stimulations of [3H]taurine release from rat sympathetic ganglia.0 aTransmitter and electrical stimulations of 3Htaurine release fro  c1994  a245–2550 v3593 aAstroglial cells release taurine in response to stimulation with neurotransmitters. This process has been studied most extensively with primary cultures of astrocytes and LRM55 glial cells. These studies have demonstrated that several transmitters can elicit release. The second messenger systems involved in activating release have been characterized (10, 15, 19). An important issue concerning all studies of this type is the applicability of results obtained with glia in culture to glia in vivo. We have chosen the rat superior cervical ganglion as a nervous tissue having the potential for exploring taurine release from glial cells in situ. The major neuronal composition of the ganglion consists of preganglionic nerve terminals providing cholinergic input and principal neurons providing noradrenergic output. The superior cervical ganglion also contains a very small population of dopamine-containing intrinsic neurons known as SIF cells (3). The glial population of the superior cervical ganglion is composed of Schwann cells responsible for myelination and satellite glia, immunoreactive to glial fibrillary acidic protein, that surround the cell bodies of the principal neurons (1, 7). Currently available data suggest that taurine is selectively taken up by the satellite glia. Autoradiographic studies have demonstrated that the ω-amino acids GABA and β-alanine are selectively accumulated by satellite glial cells in the superior cervical ganglion (5, 20), while transport studies have shown that taurine inhibits [3H]GABA uptake and that GABA inhibits [14C]taurine uptake by the superior cervical ganglion (5). The demonstration that potassium-stimulated efflux of [3H]GABA from the superior cervical ganglion is not reduced by preganglionic denervation also supports the glial localization of ω-amino acid transporters in this tissue (4).10aTritium1 aWaniewski, R., A.1 aCarp, Jonathan, S.1 aMartin, D., L.  uhttp://www.ncbi.nlm.nih.gov/pubmed/788726500429nas 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/842010302244nas a2200157   4500008004100000022001400041245005400055210005300109260001200162300001600174490000700190520180600197653001302003100002302016856004702039       1993                        eng d  a0022-307700aMonosynaptic EPSPs in primate lumbar motoneurons.0 aMonosynaptic EPSPs in primate lumbar motoneurons  c10/1993  a1585–15920 v703 a1. Homonymous and heteronymous monosynaptic composite excitatory postsynaptic potentials (EPSPs) were evaluated by intracellular recordings from 89 motoneurons innervating triceps surae (n = 59) and more distal (n = 30) muscles in 14 pentobarbital-anesthetized monkeys (Macaca nemestrina). 2. Homonymous EPSPs were found in all motoneurons tested. The mean values +/- SD for maximum EPSP amplitude of triceps surae motoneurons were 2.5 +/- 1.3, 1.8 +/- 1.3 and 4.5 +/- 2.0 mV for medial gastrocnemius, lateral gastrocnemius, and soleus motoneurons, respectively. Heteronymous EPSPs were almost always smaller than their corresponding homonymous EPSPs. 3. Triceps surae EPSP amplitude was larger in motoneurons with higher input resistance. However, this relationship was weak, suggesting that factors related to input resistance play a limited role in determining the magnitude of the EPSP. 4. The mean ratio +/- SD of the amplitude of the EPSP elicited by combined stimulation of all triceps surae nerves to the amplitude of the algebraic sum of the three individual EPSPs was 0.95 +/- 0.05. This ratio was greater in motoneurons with lower rheobase. 5. Some patterns of synaptic connectivity in the macaque are consistent with previously reported differences between primates and cat (e.g., heteronymous EPSPs elicited by medial gastrocnemius nerve stimulation in soleus motoneurons are small in macaque and other primates but large in cat). However, no overall pattern emerges from a comparison of the similarities and differences in EPSPs among species in which they have been studied (i.e., macaque, baboon, and cat). That is, there are no two species in which EPSP properties are consistently similar to each other, but different from those of the third species.(ABSTRACT TRUNCATED AT 250 WORDS)10aSynapses1 aCarp, Jonathan, S.  uhttp://www.ncbi.nlm.nih.gov/pubmed/828321602325nas 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/831723801216nas a2200229   4500008004100000022001400041245006700055210006600122260001200188300001400200490000700214520057800221653001600799653001500815653001500830653002100845653000800866100002100874700002300895700002100918856004700939       1992                        eng d  a0014-481900aConstancy of motor axon conduction time during growth in rats.0 aConstancy of motor axon conduction time during growth in rats  c08/1992  a343–3450 v903 aAxon conduction distance, conduction velocity, and conduction time were measured for individual triceps surae motoneurons in Sprague-Dawley rats weighing 230-630 g (i.e., age range 6-16 weeks). Both conduction distance (nerve length) and velocity were closely correlated with weight (r = 0.95 and r = 0.82, respectively). In contrast, conduction time did not change as weight increased nearly threefold. This striking constancy is probably due to a corresponding increase in axon diameter. It could contribute to maintenance of stable motor performance during rapid growth.10adevelopment10amotoneuron10amotor axon10anerve conduction10arat1 aChen, Xiang Yang1 aCarp, Jonathan, S.1 aWolpaw, Jonathan  uhttp://www.ncbi.nlm.nih.gov/pubmed/139714802960nas 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/169217001769nas a2200253   4500008004100000022001400041245010600055210006900161260001200230300001400242490000800256520104100264653001701305653001301322653001101335653001501346653001701361653001201378653001801390100002101408700002301429700001601452856004701468       1989                        eng d  a0304-394000aMemory traces in spinal cord produced by H-reflex conditioning: effects of post-tetanic potentiation.0 aMemory traces in spinal cord produced by Hreflex conditioning ef  c08/1989  a113–1190 v1033 aOperant conditioning of the wholly spinal, largely monosynaptic triceps surae H-reflex in monkeys causes changes in lumbosacral spinal cord that persist after removal of supraspinal influence. We evaluated the interaction between post-tetanic potentiation and these memory traces. Animals in which the triceps surae H-reflex in one leg had been increased or decreased by conditioning were deeply anesthetized, and monosynaptic reflexes to L6-S1 dorsal root stimulation were recorded before and after tetanization from both legs for 3 days after thoracic cord transection. Animals remained anesthetized throughout and were sacrificed by overdose. Reflex asymmetries consistent with the effect of H-reflex conditioning were present after transection and persisted through the 3 days of study. Tetanization affected conditioned leg and control leg reflexes similarly. This finding suggests that, while post-tetanic potentiation and probably H-reflex conditioning alter Ia synaptic transmission, the two phenomena have different mechanisms.10aconditioning10aLearning10aMemory10amotoneuron10apotentiation10aprimate10aspinal reflex1 aWolpaw, Jonathan1 aCarp, Jonathan, S.1 aLee, C., L.  uhttp://www.ncbi.nlm.nih.gov/pubmed/277985201941nas 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/249535001802nas 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/300719102025nas a2200193   4500008004100000022001400041245011400055210006900169260001200238300001400250490000700264520141800271653001201689100002301701700002101724700001501745700002401760856004701784       1983                        eng d  a0027-842400aElectrophysiological and biochemical studies on enhancement of desensitization by phenothiazine neuroleptics.0 aElectrophysiological and biochemical studies on enhancement of d  c01/1983  a310–3140 v803 aThe actions of the phenothiazines chlorpromazine, prochlorperazine, and trifluoperazine were studied on the acetylcholine receptor-ionic channel complex of frog and rat skeletal muscle and of Torpedo californica to determine their role in pharmacological desensitization and their interactions with different states of the receptor-ionic channel complex. The phenothiazines depressed the peak amplitude of spontaneous and evoked endplate currents while having negligible effect on the decay time constants. Mean channel lifetime and single channel conductance were not altered by these drugs. They also produced a frequency-dependent depression of the peak amplitude of endplate potentials evoked by repetitive microiontophoresis at the extrajunctional region. In addition, these drugs enhanced the ability of carbamoylcholine to displace 125I-labeled alpha-bungarotoxin from receptor-rich membrane preparations of T. californica when used in concentrations that had no effect on 125I-labeled alpha-bungarotoxin binding alone (10 microM). Similarly, the phenothiazines inhibited the binding of tritiated ionic channel ligands, such as phencyclidine and perhydrohistrionicotoxin, a process also enhanced by the presence of carbamoylcholine. These data suggest that the phenothiazines augment agonist-induced desensitization primarily by interacting with the receptor-ionic channel complex prior to channel opening.10aTorpedo1 aCarp, Jonathan, S.1 aAronstam, R., S.1 aWitkop, B.1 aAlbuquerque, E., X.  uhttp://www.ncbi.nlm.nih.gov/pubmed/613053101262nas 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/612624901958nas a2200169   4500008004100000022001400041245009600055210006900151260001200220300001400232490000800246520141700254653002601671100002301697700002101720856004701741       1981                        eng d  a0022-356500aModification of spinal cord transmission by an interaction of chlorpromazine and phenytoin.0 aModification of spinal cord transmission by an interaction of ch  c02/1981  a270–2740 v2163 aCat spinal cord monosynaptic activity during slow repetitive stimulation (0.2 Hz) and post-tetanic potentiation was used to evaluate the combination effects of phenytoin and chlorpromazine. The drug effects were compared in anesthetized cats with either high spinal transection or intact central nervous systems to determine whether the drugs were acting segmentally or suprasegmentally. When chlorpromazine and phenytoin were given in combination to intact animals, the depressant effect on the monosynaptic response was limited to 50% of control, which was not more than the maximum effect of either drug given alone. In spinal animals, chlorpromazine reversed the phenytoin-induced depression during 0.2 Hz stimulation, whereas only the effects of phenytoin on post-tetanic potentiation were evident after the drug combination. These results show that although phenytoin and chlorpromazine each have a depressant effect on spinal cord transmission, the combined effect is limited to a 50% decrease in intact animals. It is suggested that this occlusive drug effect demonstrates that the drug combination has a limited depressant action in the intact nervous system, an action which permits the expression of the effects of these drugs on the other elements of the reflex arc. Collectively, these actions of the drug combination are consistent with their known efficacy in treating certain cases of spasticity.10aSynaptic Transmission1 aCarp, Jonathan, S.1 aAnderson, R., J.  uhttp://www.ncbi.nlm.nih.gov/pubmed/625788501279nas a2200169   4500008004100000022001400041245006200055210005700117260001200174300001400186490000800200520080000208653001101008100002301019700002101042856004601063       1979                        eng d  a0003-978000aThe effects of phenytoin on motor function in awake cats.0 aeffects of phenytoin on motor function in awake cats  c01/1979  a139–1480 v2373 aAdult cats were monitored for their performance of a variety of motor functions before and after acute administration of phenytoin (5, 10 or 20 mg/kg) in a schedule in which each animal received all drug doses. The only significant loss in motor function was balance and coordination. Half the animals could not balance or walk along a narrow-edged beam after 20 mg/kg of phenytoin although their performance was not impaired at lower drug doses or on wider surfaces. There were no effects of phenytoin on the righting reflex, flexor reflex, muscle strength, the hopping response, the blind placing response or visually aided placing. The data suggest that phenytoin has a selective effect on higher order neuronal systems involved with balance and locomotion rather than simple reflex pathways.10aReflex1 aCarp, Jonathan, S.1 aAnderson, R., J.  uhttp://www.ncbi.nlm.nih.gov/pubmed/48567801836nas a2200193   4500008004100000022001400041245009100055210006900146260001200215300001400227490000700241520124500248653001901493653001401512653002601526100002301552700002101575856004601596       1979                        eng d  a0091-305700aSensorimotor deficits produced by phenytoin and chlorpromazine in unanesthetized cats.0 aSensorimotor deficits produced by phenytoin and chlorpromazine i  c04/1979  a513–5200 v103 aUnanesthetized adult cats were evaluated for suprasegmental reflex activity and motor skills before and after administration of chlorpromazine (0.0625–0.5 mg/kg) alone and in combination with phenytoin (20 mg/kg). The greatest deficits were seen in the tests of balance and corrdination in which half the animals failed to match their control responses after administration of chlorpromazine and phenytoin. The impairment was most noticeable with the most stringent test (walking a 4 cm wide beam), and the effects of the two drugs were additive. Although there was no effect of either drug on muscle strength, the two drugs in combination depressed the animals' motivational state, making them less willing to work against imposed loads. Neither drug, alone or in combination, altered responses to the flexor reflex, blind placing, the hopping response or visually aided placing. It is concluded that the effects of chlorpromazine and phenytoin on motor control are selective for the CNS loci which control balance and coordination. Although the two drugs produce additive responses, the deficits occur only at doses which are well above those needed for clinical efficacy and thus may not pose a problem in their long term clinical use.10aChlorpromazine10aPhenytoin10aSensorimotor deficits1 aCarp, Jonathan, S.1 aAnderson, R., J.  uhttp://www.ncbi.nlm.nih.gov/pubmed/461481