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

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.

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-motoneuron02675nas a2200325 4500008004100000022001400041245010000055210006900155260001200224300001200236490000800248520178700256653001202043653002602055653001102081653001302092653001302105653001502118653000902133653000902142653002502151653002502176100001302201700001302214700001902227700001302246700002102259700002102280856004802301 2014 eng d a1522-159800aLocomotor impact of beneficial or nonbeneficial H-reflex conditioning after spinal cord injury.0 aLocomotor impact of beneficial or nonbeneficial Hreflex conditio c03/2014 a1249-580 v1113 aWhen new motor learning changes neurons and synapses in the spinal cord, it may affect previously learned behaviors that depend on the same spinal neurons and synapses. To explore these effects, we used operant conditioning to strengthen or weaken the right soleus H-reflex pathway in rats in which a right spinal cord contusion had impaired locomotion. When up-conditioning increased the H-reflex, locomotion improved. Steps became longer, and step-cycle asymmetry (i.e., limping) disappeared. In contrast, when down-conditioning decreased the H-reflex, locomotion did not worsen. Steps did not become shorter, and asymmetry did not increase. Electromyographic and kinematic analyses explained how H-reflex increase improved locomotion and why H-reflex decrease did not further impair it. Although the impact of up-conditioning or down-conditioning on the H-reflex pathway was still present during locomotion, only up-conditioning affected the soleus locomotor burst. Additionally, compensatory plasticity apparently prevented the weaker H-reflex pathway caused by down-conditioning from weakening the locomotor burst and further impairing locomotion. The results support the hypothesis that the state of the spinal cord is a "negotiated equilibrium" that serves all the behaviors that depend on it. When new learning changes the spinal cord, old behaviors undergo concurrent relearning that preserves or improves their key features. Thus, if an old behavior has been impaired by trauma or disease, spinal reflex conditioning, by changing a specific pathway and triggering a new negotiation, may enable recovery beyond that achieved simply by practicing the old behavior. Spinal reflex conditioning protocols might complement other neurorehabilitation methods and enhance recovery.10aAnimals10aConditioning, Operant10aFemale10aH-Reflex10aLearning10aLocomotion10aMale10aRats10aRats, Sprague-Dawley10aSpinal Cord Injuries1 aChen, Yi1 aChen, Lu1 aLiu, Rongliang1 aWang, Yu1 aChen, Xiang Yang1 aWolpaw, Jonathan uhttp://www.ncbi.nlm.nih.gov/pubmed/2437128802577nas 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

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.

10aAnimals10aElectrodes, Implanted10aElectromyography10aFemale10aPubic Bone10aRats10aRats, Sprague-Dawley10aUrethra10aUrination10aUrodynamics1 aLaPallo, Brandon, K1 aWolpaw, Jonathan1 aChen, Xiang Yang1 aCarp, Jonathan, S. uhttp://www.ncbi.nlm.nih.gov/pubmed/2499089502708nas a2200373 4500008004100000022001400041245010900055210006900164260001200233300001100245490000600256520162400262653002201886653001201908653001001920653001801930653002501948653001501973653002901988653000902017653002402026653001702050653001202067653000902079653002502088653004102113653002602154100001602180700002302196700001902219700002802238700002002266856004802286 2006 eng d a1557-170X00aAnalysis of the correlation between local field potentials and neuronal firing rate in the motor cortex.0 aAnalysis of the correlation between local field potentials and n c09/2006 a6185-80 v13 a

Neuronal firing rate has been the signal of choice for invasive motor brain machine interfaces (BMI). The use of local field potentials (LFP) in BMI experiments may provide additional dendritic information about movement intent and may improve performance. Here we study the time-varying amplitude modulated relationship between local field potentials (LFP) and single unit activity (SUA) in the motor cortex. We record LFP and SUA in the primary motor cortex of rats trained to perform a lever pressing task, and evaluate the correlation between pairs of peri-event time histograms (PETH) and movement evoked local field potentials (mEP) at the same electrode. Three different correlation coefficients were calculated and compared between the neuronal PETH and the magnitude and power of the mEP. Correlation as high as 0.7 for some neurons occurred between the PETH and the mEP magnitude. As expected, the correlations between the single trial LFP and SUV are much lower due to the inherent variability of both signals.

10aAction Potentials10aAnimals10aBrain10aBrain Mapping10aElectric Stimulation10aElectrodes10aEvoked Potentials, Motor10aMale10aModels, Statistical10aMotor Cortex10aNeurons10aRats10aRats, Sprague-Dawley10aSignal Processing, Computer-Assisted10aSynaptic Transmission1 aWang, Yiwen1 aSanchez, Justin, C1 aPrincipe, Jose1 aMitzelfelt, Jeremiah, D1 aGunduz, Aysegul uhttp://www.ncbi.nlm.nih.gov/pubmed/17946745