Motor Unit Types Research Articles

Aging effects on oxidative capacity in type‐identified diaphragm muscle fibers

The diaphragm muscle (DIAm) comprises four muscle fiber/ motor unit types: Fatigue resistant type S and FR motor units with type I and IIa fibers, respectively that are recruited for ventilatory behaviors; and more fatigable type FInt and FF motor units with type IIx and/or IIb fibers that are only recruited during high force expulsive/straining behaviors of the DIAm. With advanced aging in Fischer 344 rats (F344), type IIx and/or type IIb DIAm fibers are vulnerable to sarcopenia (reductions in specific force and cross‐sectional area, CSA), while type I and IIa fibers are resilient. This is consistent with the fact that ventilatory behaviors are conserved with aging, while airway clearance behaviors are compromised. Throughout life, breathing imposes a high duty cycle (>33 %) of DIAm activity and thus, a high energy demand for type I and IIa fibers that is met by a high oxidative capacity. However, the effect of advanced age on DIAm fiber oxidative capacity has not been examined. Accordingly, we hypothesize that the oxidative capacity in type I and IIa DIAm fibers is not affected by age, whereas concomitant with sarcopenia, the oxidative capacity of type IIx and/or IIb fibers is reduced.To assess DIAm fiber oxidative capacity, we measured succinate dehydrogenase (SDH) activity in type‐identified DIAm fibers from 6, 18 and 24‐month old male and female F344 rats. Following euthanasia, the DIAm was excised and 2–3 mm strips from the mid‐costal region were dissected, stretched to optimal length and rapidly frozen in melting isopentane. Serial transverse sections (6 μm) were cut to assess fiber type (based on myosin heavy chain, MyHC isoform), cross‐sectional area (CSA) and SDH activity. For SDH, sections were incubated at 25°C for 8 min in solutions containing 0 or 80 mM succinate and 1.5 mM nitro blue tetrazolium (reaction indicator), 5 mM EDTA, 0.2 mM PMS and 0.1 mM azide in 0.1 M phosphate buffer. Images were acquired every 5 s across a 15‐min period using a 20x objective on an Olympus IX71 inverted microscope. Linearity of the SDH reaction (change in optical density‐ OD) was confirmed across the 15‐min period for each fiber type.The presence of DIAm sarcopenia was confirmed in 24‐month old rats by a 25 % decrease in specific force and a 20% decrease in type IIx and/or IIb CSA. At all ages, the SDH activity of type I and IIa fibers was higher than type IIx/IIb fibers. No age‐related difference was observed in the SDH activity of type I or IIa fibers, whereas SDH activity of type IIx and/or IIb DIAm fibers was reduced at 24 months compared to younger animals.These results underscore the remarkable vulnerability of IIx and/or IIb fibers to sarcopenia, with profound resilience in I and IIa fibers. We propose that mitochondrial abnormalities may underlie the selective vulnerability of IIx and/or IIb fibers possibly due to changes at the phrenic motor neuron level.Support or Funding InformationSupported by NIH grant AG44615This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Factors contributing to sag in unfused tetanic contractions of fast motor units in rat medial gastrocnemius

The sag phenomenon can be observed in fast motor units (MUs) as a transitional decline in force during unfused tetanic contractions; however, its mechanisms are poorly understood. The study aimed to identify in the rat muscle factors that contribute to sag in two types of fast MUs: fast fatigable (FF) and fast resistant to fatigue (FR). First, we performed mathematical decomposition of sagging tetanic contractions of FF and FR MUs into twitch-like responses to consecutive stimuli. This process indicated an increase in the amplitudes of a few initial responses (up to the 2nd–3rd for FF and up to the 2nd–7th for FR MUs), followed by a decrease in the amplitudes of later responses. In comparison to the first twitch, the relative increase in force amplitudes of the several subsequent decomposed responses was smaller, and their contraction and relaxation times were shorter for FF than for FR units, which corresponded to observed differences in their sag profiles. Additionally, after occlusion of the blood circulation, sag disappeared, but it reappeared after restoration of the blood supply. This indicates that the presence of sag depends on the proper circulation in the muscle.

Metabolic cost underlies task-dependent variations in motor unit recruitment.

Mammalian skeletal muscles are comprised of many motor units, each containing a group of muscle fibres that have common contractile properties: these can be broadly categorized as slow and fast twitch muscle fibres. Motor units are typically recruited in an orderly fashion following the 'size principle', in which slower motor units would be recruited for low intensity contraction; a metabolically cheap and fatigue-resistant strategy. However, this recruitment strategy poses a mechanical paradox for fast, low intensity contractions, in which the recruitment of slower fibres, as predicted by the size principle, would be metabolically more costly than the recruitment of faster fibres that are more efficient at higher contraction speeds. Hence, it would be mechanically and metabolically more effective for recruitment strategies to vary in response to contraction speed so that the intrinsic efficiencies and contraction speeds of the recruited muscle fibres are matched to the mechanical demands of the task. In this study, we evaluated the effectiveness of a novel, mixed cost function within a musculoskeletal simulation, which includes the metabolic cost of contraction, to predict the recruitment of different muscle fibre types across a range of loads and speeds. Our results show that a metabolically informed cost function predicts favoured recruitment of slower muscle fibres for slower and isometric tasks versus recruitment that favours faster muscles fibres for higher velocity contractions. This cost function predicts a change in recruitment patterns consistent with experimental observations, and also predicts a less expensive metabolic cost for these muscle contractions regardless of speed of the movement. Hence, our findings support the premise that varying motor recruitment strategies to match the mechanical demands of a movement task results in a mechanically and metabolically sensible way to deploy the different types of motor unit.

Is there sufficient evidence to explain the cause of sexually dimorphic behaviour in force steadiness?

Neuromuscular noise is a determining factor in the control of isometric force steadiness (FS), quantified as coefficient of variation (CV) of force around a preestablished target output. In this paper we examine sex-related differences of neural, muscular, and tendon influences on neuromuscular noise to understand FS in females and males. We use evidence from the literature to identify that CV of force is higher in females compared with males in the upper and lower body, with sex-related differences becoming less apparent with increasing age. Evaluation of sex-related physiology in tandem with results from FS studies indicate that differences in fibre type, contractile properties, and number of motor units (MUs) are unlikely contributors to differences in FS between females and males. MU type, behaviour of the population (inclusive of number of active MUs from the population), agonist-antagonist activity, maximal strength, and tendon mechanics are probable contributors to sexually dimorphic behaviour in FS. To clearly determine underlying causes of sex-related differences in FS, further study and reporting between females and males is required. Females and males are included in many studies; however, rich data on sexually dimorphic behaviour is lost when data are collapsed across sex or identified as nonsignificant without supporting values. This poses a challenge to identifying the underlying cause of females having higher CV of force than males. This review provides evidence of sexually dimorphic behaviour in FS and suggests that physiological differences between females and males effect neuromuscular noise, and in-turn contribute to sex-related differences in FS.

Biologically Guided Driver Modeling: the Stop Behavior of Human Car Drivers

This paper presents a principled approach to the modeling of human drivers—applied to stop behavior—by uniting recent ideas in cognitive science and optimal control. With respect to the former, we invoke the affordance competition hypothesis, according to which human behavior is produced by resolving the competition between action affordances that are simultaneously instantiated in response to the environment. From the theory of optimal control, we deploy motor primitives based on minimum jerk as the potential suite of actions. Furthermore, we invoke a layered control architecture, which carries out action priming and action selection sequentially, to model the biological affordance competition process. Motor output may be directed to distinct motor channels, which may be partially inhibited, e.g., to model gas pedal release saturation. Within this architecture, two types of motor units—“deceleration” acting on a gas pedal channel and “brake” acting on a brake pedal channel—are sufficient to model, with remarkable accuracy, the various phases that can be observed in human maneuvers in stopping a car, namely: gas release, gas chocked, brake, and final brake release at stop. The model is validated using experimental data collected in 16 different stop locations, from roundabouts to traffic lights. We also carry out a comparison with the well-known Intelligent Driver Model, discuss the scaling of this framework to more general driving scenarios and finally give an example application where the driver model is used, within a mirroring process, to infer the human driver intentions.

Reciprocal inhibition between motor neurons of the tibialis anterior and triceps surae in humans.

Motor neurons innervating antagonist muscles receive reciprocal inhibitory afferent inputs to facilitate the joint movement in the two directions. The present study investigates the mutual transmission of reciprocal inhibitory afferent inputs between the tibialis anterior (TA) and triceps surae (soleus and medial gastrocnemius) motor units. We assessed this mutual mechanism in large populations of motor units for building a statistical distribution of the inhibition amplitudes during standardized input to the motor neuron pools to minimize the effect of modulatory pathways. Single motor unit activities were identified using high-density surface electromyography (HDsEMG) recorded from the TA, soleus (Sol), and medial gastrocnemius (GM) muscles during isometric dorsi- and plantarflexion. Reciprocal inhibition on the antagonist muscle was elicited by electrical stimulation of the tibial (TN) or common peroneal nerves (CPN). The probability density distributions of reflex strength for each muscle were estimated to examine the strength of mutual transmission of reciprocal inhibitory input. The results showed that the strength of reciprocal inhibition in the TA motor units was fourfold greater than for the GM and the Sol motor units. This suggests an asymmetric transmission of reciprocal inhibition between ankle extensor and flexor muscles. This asymmetry cannot be explained by differences in motor unit type composition between the investigated muscles since we sampled low-threshold motor units in all cases. Therefore, the differences observed for the strength of inhibition are presumably due to a differential reciprocal spindle afferent input and the relative contribution of nonreciprocal inhibitory pathways. NEW & NOTEWORTHY We investigated the mutual transmission of reciprocal inhibition in large samples of motor units using a standardized input (electrical stimulation) to the motor neurons. The results demonstrated that the disynaptic reciprocal inhibition exerted between ankle flexor and extensor muscles is asymmetric. The functional implication of asymmetric transmission may be associated with the neural strategies of postural control.

Relationships among static strength, dynamic strength, and psychophysically determined levels of acceptable force for a pushing task and foot pedal actuation task

Static strength or psychophysical tests are commonly used to define the capabilities of a working population, but these data are not easily translated to the peak forces that users apply to products or the operational forces associated with product ease of use. This study investigated the relationships among static strength, peak forces from rapid exertions, and psychophysically determined levels of acceptable forces for 39 subjects depressing a foot pedal and pushing against a vertical surface. Peak forces were greater than static strength and psychophysically determined acceptable forces were less than static strength. The ratio of peak to static strength was greater for the pushing task than for the foot pedal task, likely because of the types of motor units recruited and the inertial effects of each exertion. Relevance to industryEngineers should be mindful when using published strength values to generate requirements for product design. The ratios among static strength, peak force, and psychophysical limits appear to vary based on task and could affect product safety, effectiveness, and ease of use.

Does a two-element muscle model offer advantages when estimating ankle plantar flexor forces during human cycling?

Traditional Hill-type muscle models, parameterized using high-quality experimental data, are often “too weak” to reproduce the joint torques generated by healthy adults during rapid, high force tasks. This study investigated whether the failure of these models to account for different types of motor units contributes to this apparent weakness; if so, muscle-driven simulations may rely on excessively high muscle excitations to generate a given force. We ran a series of forward simulations that reproduced measured ankle mechanics during cycling at five cadences ranging from 60 to 140 RPM. We generated both “nominal” simulations, in which an abstract ankle model was actuated by a 1-element Hill-type plantar flexor with a single contractile element (CE), and “test” simulations, in which the same model was actuated by a 2-element plantar flexor with two CEs that accounted for the force-generating properties of slower and faster motor units. We varied the total excitation applied to the 2-element plantar flexor between 60 and 105% of the excitation from each nominal simulation, and we varied the amount distributed to each CE between 0 and 100% of the total. Within this test space, we identified the excitation level and distribution, at each cadence, that best reproduced the plantar flexor forces generated in the nominal simulations. Our comparisons revealed that the 2-element model required substantially less total excitation than the 1-element model to generate comparable forces, especially at higher cadences. For instance, at 140 RPM, the required excitation was reduced by 23%. These results suggest that a 2-element model, in which contractile properties are “tuned” to represent slower and faster motor units, can increase the apparent strength and perhaps improve the fidelity of simulations of tasks with varying mechanical demands.

Motor unit territories in human genioglossus estimated with multichannel intramuscular electrodes.

The discharge patterns of genioglossus motor units during breathing have been well-characterized in previous studies, but their localization and territories are not known. In this study, we used two newly developed intramuscular multichannel electrodes to estimate the territories of genioglossus motor units in the anterior and posterior regions of the muscle. Seven healthy men participated. Each electrode contained fifteen bipolar channels, separated by 1 mm, and was inserted percutaneously below the chin, perpendicular to the skin, to a depth of 36 mm. Single motor unit activity was recorded with subjects awake, supine, and breathing quietly through a nasal mask for 180 s. Motor unit territories were estimated from the spike-triggered averages of the electromyographic signal from each channel. A total of 30 motor units were identified: 22 expiratory tonic, 1 expiratory phasic, 2 tonic, 3 inspiratory tonic, and 2 inspiratory phasic. Motor units appeared to be clustered based on unit type, with peak activities for expiratory units predominantly located in the anterior and superficial fibers of genioglossus and inspiratory units in the posterior region. Of these motor unit types, expiratory tonic units had the largest estimated territory, a mean 11.3 mm (SD 1.9). Estimated territories of inspiratory motor units ranged from 3 to 6 mm. In accordance with the distribution of motor unit types, the estimated territory of genioglossus motor units varied along the sagittal plane, decreasing from anterior to posterior. Our findings suggest that genioglossus motor units have large territories relative to the cross-sectional size of the muscle. NEW & NOTEWORTHY In this study, we used a new multichannel intramuscular electrode to address a fundamental property of human genioglossus motor units. We describe the territory of genioglossus motor units in the anterior and posterior regions of the muscle and show a decrease in territory size from anterior to posterior and that expiratory-related motor units have larger estimated territories than inspiratory-related motor units.

Opposite Synaptic Alterations at the Neuromuscular Junction in an ALS Mouse Model: When Motor Units Matter.

Denervation of the neuromuscular junction (NMJ) precedes the loss of motor neurons (MNs) in amyotrophic lateral sclerosis (ALS). ALS is characterized by a motor unit (MU)-dependent vulnerability where MNs with fast-fatigable (FF) characteristics are lost first, followed by fast fatigue-resistant (FR) and slow (S) MNs. However, changes in NMJ properties as a function of MU types remain debated. We hypothesized that NMJ synaptic functions would be altered precociously in an MU-specific manner, before structural alterations of the NMJ. Synaptic transmission and morphological changes of NMJs have been explored in two nerve-muscle preparations of male SOD1G37R mice and their wild-type (WT) littermates: the soleus (S and FR MU); and the extensor digitorum longus (FF MU). S, FR, and FF NMJs of WT mice showed distinct synaptic properties from which we build an MU synaptic profile (MUSP) that reports MU-dependent NMJ synaptic properties. At postnatal day 180 (P180), FF and S NMJs of SOD1 already showed, respectively, lower and higher quantal content compared with WT mice, before signs of MN death and before NMJ morphological alterations. Changes persisted in both muscles until preonset (P380), while denervation was frequent in the mutant mouse. MN death was evident at this stage. Additional changes occurred at clinical disease onset (P450) for S and FR MU. As a whole, our results reveal a reversed MUSP in SOD1 mutants and highlight MU-specific synaptic changes occurring in a precise temporal sequence. Importantly, changes in synaptic properties appear to be good predictors of vulnerability to neurodegeneration.SIGNIFICANCE STATEMENT The inadequate excitability of motor neurons and their output, the neuromuscular junctions (NMJs), has been considered a key factor in the detrimental outcome of the motor function in amyotrophic lateral sclerosis. However, a conundrum persists at the NMJ whereby persistent but incoherent opposite neurotransmission changes have been reported to take place. This article untangles this conundrum by systematically analyzing the changes in synaptic properties over the course of the disease progression as a function of the motor unit type. This temporal analysis reveals that early synaptic alterations evolve with disease progression but precede NMJ neurodegeneration. These data provide a novel framework of analysis and comparison of synaptic transmission alterations in neurodegenerative disorders.

Investigation of the HD-sEMG probability density function shapes with varying muscle force using data fusion and shape descriptors

This work presents an evaluation of the High Density surface Electromyogram (HD-sEMG) Probability Density Function (PDF) shape variation according to contraction level. On that account, using PDF shape descriptors: High Order Statistics (HOS) and Shape Distances (SD), we try to address the absence of a consensus for the sEMG non-Gaussianity evolution with force variation. This is motivated by the fact that PDF shape information are relevant in physiological assessment of the muscle architecture and function, such as contraction level classification, in complement to classical amplitude parameters. Accordingly, both experimental and simulation studies are presented in this work. For data fusion, the watershed image processing technique was used. This technique allowed us to find the dominant PDF shape variation profiles from the 64 signals. The experimental protocol consisted of three isometric isotonic contractions of 30, 50 and 70% of the Maximum Voluntary Contraction (MVC). This protocol was performed by six subjects and recorded using an 8 × 8 HD-sEMG grid. For the simulation study, the muscle modeling was done using a fast computing cylindrical HD-sEMG generation model. This model was personalized by morphological parameters obtained by sonography. Moreover, a set of the model parameter configurations were compared as a focused sensitivity analysis of the PDF shape variation. Further, monopolar, bipolar and Laplacian electrode configurations were investigated in both experimental and simulation studies. Results indicated that sEMG PDF shape variations according to force increase are mainly dependent on the Motor Unit (MU) spatial recruitment strategy, the MU type distribution within the muscle, and the used electrode arrangement. Consequently, these statistics can give us an insight into non measurable parameters and specifications of the studied muscle primarily the MU type distribution.

Modifying motor unit territory placement in the Fuglevand model.

The Fuglevand model is often used to address challenging questions in neurophysiology; however, there are elements of the neuromuscular system unaccounted for in the model. For instance, in some muscles, slow and fast motor units (MUs) tend to reside deep and superficially in the muscle, respectively, necessarily altering the development of surface electromyogram (EMG) power during activation. Thus, the objective of this study was to replace the randomized MU territory (MUT) placement algorithm in the Fuglevand model with an optimized method capable of reflecting these observations. To accomplish this, a weighting term was added to a previously developed optimization algorithm to encourage regionalized MUT placement. The weighting term consequently produced significantly different muscle fibre type content in the deep and superficial portions of the muscle. The relation between simulated EMG and muscle force was found to be significantly affected by regionalization. These changes were specifically a function of EMG power, as force was unaffected by regionalization. These findings suggest that parameterizing MUT regionalization will allow the model to produce a larger variety of EMG-force relations, as is observed physiologically, and could potentially simulate the loss of specific MU types as observed in ageing and clinical populations.

Motor unit and muscle fiber type grouping after peripheral nerve injury in the rat

Muscle unit (MU) fibers innervated by one motoneuron and corresponding muscle fiber types are normally distributed in a mosaic. We asked whether, 4–8months after common peroneal nerve transection and random surgical alignment of nerve stumps in rat tibialis anterior muscles 1) reinnervated MU muscle and muscle fiber type clumping is invariant and 2) slow and fast motoneurons regenerate their nerve fibers within original endoneurial pathways. MU contractile forces were recorded in vivo, the MUs classified into types according to their contractile speed and fatigability, and one MU subjected to alternate exhaustive stimulation-recovery cycles to deplete glycogen for histochemical MU fiber recognition and enumeration, and muscle fiber typing. MU muscle fibers occupied defined territories whose size increased with MU force and muscle fiber numbers in normal and reinnervated muscles. The reinnervated MU muscle fiber territories were significantly smaller, the fibers clumped within 1–3 groups in 90% of the MUs, and each fiber lying adjacent to another significantly more frequently. Most reinnervated slow muscle fibers were normally located in the deep muscle compartment but substantial numbers were located abnormally in the superficial compartment. Our findings that well reinnervated muscle fibers clump in small muscles contrast with our earlier findings of clumping in large muscles only when reinnervated MU numbers were significantly reduced. We conclude that fiber type clumping is predictive of muscle reinnervation in small but not large muscles. In the latter muscles, clumping is more indicative of sprouting after partial nerve injuries than of muscle reinnervation after complete nerve injuries.

Contractile properties of motor units and expression of myosin heavy chain isoforms in rat fast-type muscle after volitional weight-lifting training.

Dynamic resistance training increases the force and speed of muscle contraction, but little is known about modifications to the contractile properties of the main physiological types of motor units (MUs) that contribute to these muscle adaptations. Although the contractile profile of MU muscle fibers is tightly coupled to myosin heavy chain (MyHC) protein expression, it is not well understood if MyHC transition is a prerequisite for modifications to the contractile characteristics of MUs. In this study, we examined MU contractile properties, the mRNA expression of MyHC, parvalbumin, and sarcoendoplasmic reticulum Ca2+ pump isoforms, as well as the MyHC protein content after 5 wk of volitional progressive weight-lifting training in the medial gastrocnemius muscle in rats. The training had no effect on MyHC profiling or Ca2+-handling protein gene expression. Maximum force increased in slow (by 49%) and fast (by 21%) MUs. Within fast MUs, the maximum force increased in most fatigue-resistant and intermediate but not most fatigable MUs. Twitch contraction time was shortened in slow and fast fatigue-resistant MUs. Twitch half-relaxation was shortened in fast most fatigue-resistant and intermediate MUs. The force-frequency curve shifted rightward in fast fatigue-resistant MUs. Fast fatigable MUs fatigued less within the initial 15 s while fast fatigue-resistant units increased the ability to potentiate the force within the first minute of the standard fatigue test. In conclusion, at the early stage of resistance training, modifications to the contractile characteristics of MUs appear in the absence of MyHC transition and the upregulation of Ca2+-handling genes.

Estimation of the error between experimental tetanic force curves of MUs of rat medial gastrocnemius muscle and their models by summation of equal successive contractions

More accurate muscle models require appropriate modelling of individual twitches of motor units (MUs) and their unfused tetanic contractions. It was shown in our previous papers, using a few MUs, that modelling of unfused tetanic force curves by summation of equal twitches is not accurate, especially for slow MUs. The aim of this study was to evaluate this inaccuracy using a statistical number of MUs of the rat medial gastrocnemius muscle (15 of slow, 15 of fast resistant and 15 of fast fatigable type). Tetanic contractions were evoked by trains of 41 stimuli at random interpulse intervals and different mean frequencies, resembling discharge patterns observed during natural muscle activity. The tetanic curves were calculated by the summation of equal twitches according to the respective experimental patterns. The previously described 6-parameter analytical function for twitch modelling was used. Comparisons between the experimental and the modelled curves were made using two coefficients: the fit coefficient and the area coefficient. The errors between modelled and experimental tetanic forces were substantially different between the three MU types. The error was the most significant for slow MUs, which develop much higher forces in real contractions than could be predicted based on the summation of equal twitches, while the smallest error was observed for FF MUs – their recorded tetanic forces were similar to those predicted by modelling. The obtained results indicate the importance of the inclusion of the type-specific non-linearity in the summation of successive twitch-like contractions of MUs in order to increase the reliability of modelling skeletal muscle force.

Inappropriate interpretation of surface EMG signals and muscle fiber characteristics impedes understanding of the control of neuromuscular function

as the final common pathway from the nervous system to muscle, the motor unit transmits an activation signal generated by the nervous system to engage the contractile proteins and produce the muscle forces needed for reflex responses, automatic behaviors, and voluntary actions ([11][1]). The net

Homeostatic dysregulation in membrane properties of masticatory motoneurons compared with oculomotor neurons in a mouse model for amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative motoneuron disease with presently no cure. Motoneuron (MN) hyperexcitability is commonly observed in ALS and is suggested to be a precursor for excitotoxic cell death. However, it is unknown whether hyperexcitability also occurs in MNs that are resistant to degeneration. Second, it is unclear whether all the MNs within homogeneous motor pools would present similar susceptibility to excitability changes since high-threshold MNs innervating fast fatigable muscle fibers selectively degenerate compared with low-threshold MNs innervating fatigue resistant slow muscle fibers. Therefore, we concurrently examined the excitability of ALS-vulnerable trigeminal motoneurons (TMNs) controlling jaw musculature and ALS-resistant oculomotor neurons (OMNs) controlling eye musculature in a well studied SOD1(G93A) ALS mouse model using in vitro patch-clamp electrophysiology at presymptomatic ages P8-P12. Our results show that hyperexcitability is not a global change among all the MNs, although mutant SOD1 is ubiquitously expressed. Instead, complex changes occur in ALS-vulnerable TMNs based on motor unit type and discharge characteristics. Firing threshold decreases among high-threshold TMNs and increases in a subpopulation of low-threshold TMNs. The latter group was identified based on their linear frequency-current responses to triangular ramp current injections. Such complex changes in MN recruitment were absent in ALS-resistant OMNs. We simulated the observed complex changes in TMN excitability using a computer-based jaw closer motor pool model. Model results suggest that hypoexcitability may indeed represent emerging disease symptomology that causes resistance in muscle force initiation. Identifying the cellular and molecular properties of these hypoexcitable cells may guide effective therapeutic strategies in ALS.

Spinal mechanisms may provide a combination of intermittent and continuous control of human posture: predictions from a biologically based neuromusculoskeletal model.

Several models have been employed to study human postural control during upright quiet stance. Most have adopted an inverted pendulum approximation to the standing human and theoretical models to account for the neural feedback necessary to keep balance. The present study adds to the previous efforts in focusing more closely on modelling the physiological mechanisms of important elements associated with the control of human posture. This paper studies neuromuscular mechanisms behind upright stance control by means of a biologically based large-scale neuromusculoskeletal (NMS) model. It encompasses: i) conductance-based spinal neuron models (motor neurons and interneurons); ii) muscle proprioceptor models (spindle and Golgi tendon organ) providing sensory afferent feedback; iii) Hill-type muscle models of the leg plantar and dorsiflexors; and iv) an inverted pendulum model for the body biomechanics during upright stance. The motor neuron pools are driven by stochastic spike trains. Simulation results showed that the neuromechanical outputs generated by the NMS model resemble experimental data from subjects standing on a stable surface. Interesting findings were that: i) an intermittent pattern of muscle activation emerged from this posture control model for two of the leg muscles (Medial and Lateral Gastrocnemius); and ii) the Soleus muscle was mostly activated in a continuous manner. These results suggest that the spinal cord anatomy and neurophysiology (e.g., motor unit types, synaptic connectivities, ordered recruitment), along with the modulation of afferent activity, may account for the mixture of intermittent and continuous control that has been a subject of debate in recent studies on postural control. Another finding was the occurrence of the so-called “paradoxical” behaviour of muscle fibre lengths as a function of postural sway. The simulations confirmed previous conjectures that reciprocal inhibition is possibly contributing to this effect, but on the other hand showed that this effect may arise without any anticipatory neural control mechanism.

IH activity is increased in populations of slow versus fast motor axons of the rat.

Much is known about the electrophysiological variation in motoneuron somata across different motor units. However, comparatively less is known about electrophysiological variation in motor axons and how this could impact function or electrodiagnosis in healthy or diseased states. We performed nerve excitability testing on two groups of motor axons in Sprague–Dawley rats that are known to differ significantly in their chronic daily activity patterns and in the relative proportion of motor unit types: one group innervating the soleus (“slow motor axons”) and the other group innervating the tibialis anterior (“fast motor axons”) muscles. We found that slow motor axons have significantly larger accommodation compared to fast motor axons upon application of a 100 ms hyperpolarizing conditioning stimulus that is 40% of axon threshold (Z = 3.24, p = 0.001) or 20% of axon threshold (Z = 2.67, p = 0.008). Slow motor axons had larger accommodation to hyperpolarizing currents in the current-threshold measurement (-80% Z = 3.07, p = 0.002; -90% Z = 2.98, p = 0.003). In addition, we found that slow motor axons have a significantly smaller rheobase than fast motor axons (Z = -1.99, p = 0.047) accompanied by a lower threshold in stimulus-response curves. The results provide evidence that slow motor axons have greater activity of the hyperpolarization-activated inwardly rectifying cation conductance (IH) than fast motor axons. It is possible that this difference between fast and slow axons is caused by an adaptation to their chronic differences in daily activity patterns, and that this adaptation might have a functional effect on the motor unit. Moreover, these findings indicate that slow and fast motor axons may react differently to pathological conditions.

Changes in motor unit properties in SOD1 (G93A) rats

In amyotrophic lateral sclerosis (ALS), progressive death of motor neurons results in denervation and reinnervation of muscles. It is not clear how ALS affects the properties of motor units (MUs). Properties of single MUs in the medial gastrocnemius (MG) muscle of rats bearing the human mutated superoxide dismutase gene type 1 (SOD1) were determined at 3 stages: asymptomatic (ALS I); early symptomatic (ALS II); and terminal (ALS III). In ALS II, higher proportions of FF (fast fatigable) and S (slow) MUs were observed, whereas in ALS III higher percentages of S and lower percentages of FF MUs were noted compared with controls. S motor neurons reinnervated fast muscle fibers, and those MUs gained some properties of fast MUs, including lower fatigue resistance, greater force generation, and higher action potential amplitudes. Changes in MU properties of SOD1 rats have progressive and multidirectional character and speed depending on the MU type.