Organization Of Motor Units Research Articles

Reciprocal and coactivation commands at the level of individual motor units in an extrinsic finger flexor-extensor muscle pair.

We explored the synergic organization of motor units in extrinsic finger muscles, flexor digitorum superficialis (FDS), and extensor digitorum communis (EDC). Healthy subjects produced accurate cyclical force by pressing with the middle phalanges of one of the three fingers (Index, Middle, and Ring) and all three together. Two wireless sensor arrays were used to record and identify motor unit action potentials in FDS and EDC. Stable motor unit groups were identified within each muscle and across both muscles. Analysis of motor units combined over the two muscles showed one of the first two motor unit groups with consistently opposite signs of the loading factors for the FDS and EDC motor units, and the other group with consistently same signs of the loading factors for the two muscles. We interpret the two motor unit groups as reflections of the reciprocal and co-activation commands within the theory of control with spatial referent coordinates. Force changes within the cycle were primarily associated with the modulation of the co-activation motor unit group. Analysis of inter-cycle variance within the spaces of motor unit groups defined for FDS and EDC separately showed force-stabilizing synergies across both single-finger and three-finger tasks. In contrast, analysis within the motor unit groups defined across both muscles failed to show force-stabilizing synergies. We interpret these results as a reflection of the trade-off across levels within a hierarchical control system.

Synergies at the level of motor units in single-finger and multi-finger tasks.

We explored the organization of motor units recorded in the flexor digitorum superficialis into stable groups (MU-modes) and force-stabilizing synergies in spaces of MU-modes. Young, healthy participants performed one-finger and three-finger accurate cyclical force production tasks. Two wireless sensor arrays (Trigno Galileo, Delsys, Inc.) were placed over the proximal and distal portions of the muscle for surface recording and identification of motor unit action potentials. Principal component analysis with Varimax rotation and factor extraction was used to identify MU-modes. The framework of the uncontrolled manifold hypothesis was used to analyze inter-cycle variance in the space of MU-modes and compute the index of force-stabilizing synergy. Multiple linear regression between the first MU-mode in the three-finger task and the first MU-modes in the three single-finger tasks showed no differences between the data recorded by the two electrodes suggesting that MU-modes were unlikely to be synonymous with muscle compartments. Multi-MU-mode synergies stabilizing task force were documented across all tasks. In contrast, there were no force-stabilizing synergies in the three-finger task analyzed in the space of individual finger forces. Our results confirm the synergic organization of motor units in single-finger tasks and, for the first time, expand this result to multi-finger tasks. We offer an interpretation of the findings within the theoretical scheme of control with spatial referent coordinates expanded to the analysis of individual motor units. The results confirm trade-offs between synergies at different hierarchical levels and expand this notion to intra-muscle synergies.

Motor unit number estimation in adult patients with spinal muscular atrophy treated with nusinersen.

The aim was to assess the organization and short-term changes of motor units in adult patients with spinal muscular atrophy (SMA) treated with nusinersen. In this single-centre cross-sectional and longitudinal study 15 adult patients with SMA type 3 were assessed and compared to 15 age-matched healthy controls and nine patients with amyotrophic lateral sclerosis. Moreover, 10 patients with SMA were followed up after 4-8months. All patients were investigated clinically and by the motor unit number estimation method MScanFit of the abductor pollicis brevis muscle. The number of motor units (p<0.001) was significantly lower in patients with SMA compared to healthy controls at study entry. Mean unit amplitude, median amplitude and largest unit (p<0.001) were significantly increased in patients with SMA. Patients with amyotrophic lateral sclerosis showed a significant reduction of compound muscle action potential (p=0.005) and number of motor units (p=0.03) compared to patients with SMA, accompanied by a larger median amplitude (p=0.03). A prospective analysis identified patients with the ability to walk to improve the number of motor units (p=0.046) accompanied by a decreased median amplitude (p=0.03). Electrophysiological measures showed a moderate to strong correlation with clinical scores. Patients with SMA show loss of motor units in distal muscles. MScanFit variables indicate that compound muscle action potential amplitudes are maintained by collateral sprouting. Prospective analyses suggest that milder affected adult patients with SMA preferentially benefit from nusinersen treatment through recovery of smaller motor units. Correlations with clinical scores underline the potential of MScanFit as a surrogate marker.

Breathing: Motor Control of Diaphragm Muscle.

Breathing occurs without thought but is controlled by a complex neural network with a final output of phrenic motor neurons activating diaphragm muscle fibers (i.e., motor units). This review considers diaphragm motor unit organization and how they are controlled during breathing as well as during expulsive behaviors.

New features for scanned bioelectrical activity of motor unit in health and disease

Abstract The present study aims to find new features that support the differential diagnosis of neuromuscular diseases. Scanning EMG is an experimental method developed for understanding the motor unit organization and for observing temporal and spatial characteristics of motor unit’s electrical activity. A motor unit consists of a motor neuron and muscle fibers that are innervated by its motor neuron. Both simulation and biological data on neuromuscular diseases are considered in this study. Biological data were acquired from 3 patients with neurogenic involvement (2 with poliomyelitis sequela and 1 with spinal muscular atrophy), 2 patients with myopathy (1 with inflammatory myopathy and 1 with muscular dystrophy) and 4 healthy participants. Seven features are extracted by specifications of neuromuscular diseases and characteristics of EMG signals. These features are maximum amplitude, spike duration, the number of peaks, maximum amplitude x spike duration, number of peaks x spike duration, the ratio of the power outside the activity corridor to the power inside the activity corridor and the number of peaks outside of the activity corridor. The autocorrelation function of the sum of scanning EMG signals is effective in determining the activity corridor of these signals and the spike duration can be determined more easily by using the activity corridor. Wavelet transform based noise reduction and the windowing method are proposed for calculating the features correctly. By this method, spike duration and the number of peaks should be able to be calculated more precisely. It is confirmed that if the signals are filtered by a high pass filter with a cut off frequency of 2 KHz, the calculation of the number of peaks should be easier. While maximum amplitude and maximum amplitude times spike duration are found to be significant for diagnosing neurogenic diseases, other features are found to be significant for all groups by ANOVA test. It is determined that which features are more effective for differential diagnosis and the dataset that contains normal people and patients is classified using multi-layer perceptron (MLP), radial basis function network (RBF), support vector machines (SVM) and k nearest neighbor algorithm (k-NN). The best accuracy is obtained as 85% with MLP network.

Mosaic Organization of Body Pattern Control in the Optic Lobe of Squids

Cephalopods in nature undergo highly dynamic skin coloration changes that allow rapid camouflage and intraspecies communication. The optic lobe is thought to play a key role in controlling the expansion of the chromatophores that generate these diverse body patterns. However, the functional organization of the optic lobe and neural control of the various body patterns by the optic lobe are largely unknown. We applied electrical stimulation within the optic lobe to investigate the neural basis of body patterning in the oval squid, <i>Sepioteuthis lessoniana</i>. Most areas in the optic lobe mediated predominately ipsilateral expansion of chromatophores present on the mantle, but not on the head and arms; furthermore, the expanded areas after electrical stimulation were positively correlated with an increase in stimulating voltage and stimulation depth. These results suggest a unilaterally dominant and vertically converged organization of the optic lobe. Furthermore, analyzing 14 of the elicited body pattern components and their corresponding stimulation sites revealed that the same components can be elicited by stimulating different parts of the optic lobe and that various subsets of these components can be coactivated by stimulating the same area. These findings suggest that many body pattern components may have multiple motor units in the optic lobe and that these are organized in a mosaic manner. The multiplicity associated with the nature of the neural controls of these components in the cephalopod brain thus reflects the versatility of the individual components during the generation of diverse body patterns. <b>SIGNIFICANCE STATEMENT</b> Neural control of the dynamic body patterning of cephalopods for camouflage and intraspecies communication is a fascinating research topic. Previous studies have shown that the optic lobe is the motor command center for dynamic body patterning. However, little is known about its neural organization and the mechanisms underlying its control of body pattern generation. By electrically stimulating the optic lobe of the oval squids and observing their body pattern changes, surprisingly, we found that there is no somatotopic organization of motor units. Instead, many of these components have multiple motor units within the optic lobe and are organized in a mosaic manner. The present work reveals a novel neural control of dynamic body patterning for communication in cephalopods.

Mosaic Organization of Body Pattern Control in the Optic Lobe of Squids.

Neural control of the dynamic body patterning of cephalopods for camouflage and intraspecies communication is a fascinating research topic. Previous studies have shown that the optic lobe is the motor command center for dynamic body patterning. However, little is known about its neural organization and the mechanisms underlying its control of body pattern generation. By electrically stimulating the optic lobe of the oval squids and observing their body pattern changes, surprisingly, we found that there is no somatotopic organization of motor units. Instead, many of these components have multiple motor units within the optic lobe and are organized in a mosaic manner. The present work reveals a novel neural control of dynamic body patterning for communication in cephalopods.

Synaptic organization of tonic motor units in vertebrates

The features of synaptic organization of tonic motor units in vertebrates, which are widely represented in amphibians and reptiles but preserved only as muscular systems serving sensory organs in mammals, are reviewed. Based on the previous classical works, the comparative description of innervation and neurotransmitter secretion of tonic muscular systems is given. The data on synaptic organization of tonic muscles obtained in the studies that were continued after a 20-year break and published in the past few years are discussed.

Electrophysiological method to examine muscle fiber architecture in the upper lip in cleft-lip patients

The upper lip's musculature comprises several muscle fiber groups with different spatial orientations for various lip movements. In the past, it has not been possible to describe these various groups and their motor units in detail with traditional methods of electromyography (EMG). The purpose of this investigation was to create a viable method for studying the architecture of upper-lip muscle fibers in patients with surgically closed cleft lip by refining the design of a flexible electrode array for multichannel EMG. Calibrated perioral photographs of 36 adult subjects were used to determine the basic geometry of an electrode array for use on different facial shapes. A total of 256 chloride silver electrodes, 1 mm in diameter, were distributed over this geometry to form a grid with interelectrode distances of 2.5 mm. Technical implementation of the electrode array was based on a modified technique used for flexible printed circuit boards. A double-sided adhesive tape with perforations was used to apply the array to the skin in the upper-lip area. Surface EMG signals were recorded while the subjects were performing various lip movements and exerting specific lip forces. The latter were recorded with a specially developed transducer. Despite an extremely dense grid of electrodes associated with downsized contacts, the electrode array could be precisely applied to the perforated adhesive tape. The electrode array remained firmly attached to the skin even during extensive lip movements. The recorded EMG signals offered high baseline stability and a strong signal-to-noise ratio, thus, allowing us to extract individual motor unit action potentials (MUAPs). Spatiotemporal tracking of MUAPs succeeded in demonstrating the course of muscle fibers belonging to individual motor units. Pilot measurements taken on subjects with surgically closed unilateral cleft lip revealed an asymmetric distribution of muscle activity surrounding the closed cleft-lip segments. Our refined noninvasive electrophysiological method is capable of providing detailed information about muscle fiber architecture and the position, size, and organization of motor units in the lip area. It is thus feasible to conduct further studies to analyze differences in muscle morphology and motor control between surgically treated cleft-lip patients and noncleft individuals.

The innervation and organization of motor units in a series-fibered human muscle: the brachioradialis

We studied the innervation and organization of motor units in the brachioradialis muscle of 25 normal human subjects. We recorded intramuscular EMG signals at points separated by 15 mm along the proximodistal muscle axis during moderate isometric contractions, identified from 27 to 61 (mean 39) individual motor units per subject using EMG decomposition, and estimated the locations of the endplates and distal muscle/tendon junctions from the motor-unit action potential (MUAP) propagation patterns and terminal standing waves. In three subjects all the motor units were innervated in a single endplate zone. In the other 22 subjects, the motor units were innervated in 3-6 (mean 4) distinct endplate zones separated by 15-55 mm along the proximodistal axis. One-third of the motor units had fibers innervated in more than one zone. The more distally innervated motor units had distinct terminal waves indicating tendonous termination, while the more proximal motor units lacked terminal waves, indicating intrafascicular termination. Analysis of blocked MUAP components revealed that 19% of the motor units had at least one doubly innervated fiber, i.e., a fiber innervated in two different endplate zones by two different motoneurons, and thus belonging to two different motor units. These results are consistent with the brachioradialis muscle having a series-fibered architecture consisting of multiple, overlapping bands of muscle fibers in most individuals and a simple parallel-fibered architecture in some individuals.

Force estimation from ensembles of Golgi tendon organs

Golgi tendon organs (GTOs) located in the skeletal muscles provide the central nervous system with information about muscle tension. The ensemble firing of all GTO receptors in the muscle has been hypothesized to represent a reliable measure of the whole muscle force but the precision and accuracy of that information are largely unknown because it is impossible to record activity simultaneously from all GTOs in a muscle. In this study, we combined a new mathematical model of force sampling and transduction in individual GTOs with various models of motor unit (MU) organization and recruitment simulating various normal, pathological and neural prosthetic conditions. Our study suggests that in the intact muscle the ensemble GTO activity accurately encodes force information according to a nonlinear, monotonic relationship that has its steepest slope for low force levels and tends to saturate at the highest force levels. The relationship between the aggregate GTO activity and whole muscle tension under some pathological conditions is similar to one seen in the intact muscle during rapidly modulated, phasic excitation of the motor pool (typical for many natural movements) but quite different when the muscle is activated slowly or held at a given force level. Substantial deviations were also observed during simulated functional electrical stimulation.

The histochemical profile of the rat extensor digitorum longus muscle differentiates after birth and dedifferentiates in senescence.

Age dependent motor unit dedifferentiation is a key component of impaired muscle function in advanced age. Here, we tested the hypothesis that rat muscle histochemical profile during the lifespan of an individual has an age-specific pattern since comprehensive longitudinal studies of muscle differentiation after birth and dedifferentiation in advanced age are scarce. Our results show that extensor digitorum longus muscle (EDL) is comprised only of two fiber types after birth, type slow-oxidative (SO) and type SDH-intermediate (SDH-INT), the latter being indicative for the presence of polyneuronal innervation. In contrast to the constantly growing cross-sectional area of the muscle fibers, a dramatic decrease in SDH-INT proportion occurs between day 14 and 21 after birth resulting in a complete loss of fiber type SDH-INT at the age of 90 days (p<0.05). At the age of 270 days, the fiber type composition of rat EDL dedifferentiates as shown by the reappearance of the SDH-INT type with a further increase at the age of 540 days (p<0.05). These changes in histochemical fiber type spectra are brought about by fiber type conversion within the fast twich fibers. The findings of the present study provide further evidence that fiber type conversion is a basic mechanism leading to motor unit differentiation and dedifferentiation during ontogenesis. Fiber type conversion shows a distinct time specific pattern and is also characteristic for motor unit regeneration after peripheral nerve repair. Factors that influence fiber type conversion and thereby motor unit organization may provide a future therapeutic option to enhance the regenerative capacity of motor units.

Graft repair of the peroneal nerve restores histochemical profile after long‐term reinnervation of the rat extensor digitorum longus muscle in contrast to end‐to‐end repair

Declining motor function is a prominent feature of ageing physiology. One reason for this is a reduction in plasticity that normally compensates for ongoing reorganization of motor units under physiological conditions. Previous work from our laboratory has shown that microsurgical repair of the transected peroneal nerve is followed by considerable changes in the histochemical profile of the reinnervated extensor digitorum longus (EDL) muscle and that these changes are dependent on both the time and the type of nerve repair. At 6 months postoperatively, a trend toward reversibility could be discerned. In the present work, we analysed the long-term reorganization of histochemical motor unit distribution patterns 15 months after performing either end-to-end repair or grafting of the peroneal nerve in 3-month-old rats. In addition, the EDL muscles of an age-matched control group (age 18 months) were analysed for age-dependent changes. We observed a loss of histochemical organization of motor units leading to an additional fibre type (SDH-INT) in the control group. Fifteen months after end-to-end repair, the histochemical profile showed a decrease in fibre type IIA and an increase in fibre type SDH-INT (P < 0.05), indicating a profound histochemical disorganization of motor units. In contrast, nerve grafting largely restored the histochemical profile of reinnervated EDL muscles. Fibre type grouping was present after both types of nerve repair. These findings show that reorganization of the histochemical profile in reinnervated muscles is dependent on the time and type of nerve repair and is long lasting. In this study, grafting provided superior results compared with end-to-end repair. These long-term results after peripheral nerve repair are influenced by age-dependent changes. Accordingly, nerve repair reduces the normal functional plasticity of motor unit organization. This reduction is enhanced by increasing age.

Clinical impact of single-fiber electromyography.

The major clinical impact of single-fiber electromyography has been from its role in confirming, or excluding, the diagnosis of myasthenia gravis (MG). Jitter measurements also have a clinical role in demonstrating changes in disease severity in patients with MG and Lambert-Eaton myasthenic syndrome, in demonstrating subtle changes in motor unit architecture and physiology in patients with nerve and muscle diseases, and in demonstrating the remote effects of locally injected botulinum toxin. In addition to these clinical roles, the ability to identify the activity from single muscle fibers makes it possible to mark the discharges of single motor units. This, along with information gained by jitter and fiber-density measurements, has uniquely increased our understanding of motor unit organization and function in normal and disease states.

Neuromuscular organization of avian flight muscle: Morphology and contractile properties of motor units in the pectoralis (pars thoracicus) of pigeon (Columba livia).

We used acid digestion and glycogen depletion to determine fascicle organization, fiber morphology, and physiological and anatomical features of individual motor units of an in-series muscle, the pectoralis (pars thoracicus) of the pigeon (Columba livia). Most fascicles are attached at one end to connective tissue. Average fiber length in the four regions examined range from 42% to 66% of average fascicle length. More than 65% of fibers are blunt at one end of a fascicle and taper intrafascicularly. Fibers with blunt-blunt endings range from 13% to 31% of the population in different regions; taper-taper fibers range from 2% to 17%. Pigeon pectoralis fibers are distinguished histochemically into fast-twitch glycolytic (FG) and fast-twitch oxidative-glycolytic (FOG) populations. Three units composed of FG fibers (FG units) contract more quickly than three units composed of FOG fibers (FOG units) (range 31-37 vs 47-62 msec), produce more tetanic force (0.11-0.32 vs 0.02-0.05 N) and are more fatigable (<18% initial force vs >50% after repeated stimulation). Most motor units are confined to one of the four muscle regions. Territory of two FOG units is <30% of parent fascicle length. Territories of other units spanned parent fascicles; most fibers in these units do not extend the full fascicle length. Compared to FG units, FOG units have lower maximum innervation ratios and density indices (ratio of depleted/total FOG fibers in territory 8-14% vs 58-76% for FG units). These differences support the hypothesis that FG units are organized to produce substantial force and power for takeoff, landing and other ballistic movements whereas FOG units are suited for sustained flight when power requirements are reduced. Implications of findings for understanding the control of in-series muscles and the use of connective tissue elastic elements during wing movements are discussed. J.Morphol. 236:179-208, 1998. © 1998 Wiley-Liss, Inc.

Regeneration of specific innervation in Xenopus pectoralis muscle.

We investigated the motor unit organization and precision of reinnervation in the Xenopus pectoralis muscle following different manipulations, including crush or section of the posterior pectoralis nerve, foreign nerve innervation, and crush coupled with activity modulation or block. Most fibers have two neuromuscular junctions, and multielectrode recordings were used to identify the axonal origin of all inputs to both junctions on most or all fibers covering about 25% of the muscle surface. Following simple nerve crush, a highly organized innervation pattern was restored, indistinguishable from the normal pattern, including selective innervation of fibers of similar input resistance (R(in)), compact motor unit organization, and high incidence of exclusive innervation of both end plates on each fiber by the same axon (distributed mononeuronal innervation, or a/a pattern). Initial reinnervation was equally precise when nerve conduction in the regenerating nerve was blocked by tetrodotoxin. More distant or repeated nerve crush or nerve section delayed and reduced the precision of reinnervation, but the majority of fibers still received input to both end plates by the same axon, often in combination with others. A foreign nerve, the pectoralis sternalis, which in its own muscle forms only single end plates, showed less precise reinnervation, but still had an incidence of a/a innervation far above chance. These data imply the expression and recognition of remarkably precise chemospecific cues even in mature animals, superimposed on which is a further refinement by synapse elimination, probably based on an activity-dependent process.

Historical perspective: a framework for interpreting pathobiological ideas on human muscle fatigue.

The flow of ideas on the causes of human muscle fatigue appear to have been established in the literature during the last century. Critical analysis had to await innovative experimental designs or techniques. Progress has come particularly from the recognition of inconsistencies, particularly in clinical conditions in which there are alterations in the supply of energy or contractile function. While there is a continuing search for a unique cause of fatigue, much evidence points to there being different causes according to the type of muscular activity or clinical condition. "Nature's experiments" (patients exhibiting isolated defects of function or metabolism) offer unique opportunities for understanding the relative importance of particular levels of metabolic organization or physiological control. Theories of limiting biochemical processes and the Ca- kinetic basis of electromechanical coupling defects are both essentially "single-cell" models of fatigue. Functional requirements appear to determine the diversity of structure and organization of motor units. This would suggest that a "muscle cell population" approach would take into account the consequences of disease altering the number, type of functioning fibers or intrinsic strength of individual fibers. A graphical model is offered to allow a possible interpretation of the cause of fatigue in different forms of exercise and clinical conditions.

Biochemical organization of single motor units in two multi-tendoned muscles of the cat distal forelimb.

In anesthetized cats single motor units (MUs) of the extensor carpi ulnaris (ECU) and extensor digitorum communis (EDC) muscles were selectively activated by stimulation of cervical ventral root filaments. The distribution of force developed by single MUs at the four distal tendons of the EDC muscle and at three portions of the distal tendon of the ECU muscle was analysed. In general, single MUs of both muscles distributed force over all tendons in a unimodal pattern, with the maximal force levels generated at one specific tendon which was termed the best-tendon. Distributions of force were quantitatively described by a parameter representing the mean direction of force output (output-index) and a further one representing the dispersion of force over the distal tendons (divergence). Generally, these parameters and the best-tendon remained stable when a MU was stimulated at different frequencies, but varied from MU to MU. Despite the general stability of the force distribution, slight systematic changes were regularly found in EDC MUs, when they developed a higher amount of force due to a higher frequency of stimulation: the relative amount of force at the best-tendon increased; e.g. the MUs got more selective for the best-tendon. These changes were partly due to overcoming mechanical cross-coupling between neighbouring compartments of the EDC muscle. Such changes of force distribution were only found in a part of the ECU MUs; other ECU MUs did not change their force distribution at all or became less selective for the best-tendon. The phenomenon that MUs of multi-tendoned muscles distribute their force output to the distal tendons in specific patterns is probably due to mechanical partitioning of the parent muscles: the localization of spatial territories of MUs within different anatomical muscle compartments should correspond to the best-tendon. Complex mechanisms allowing passive transmission of force from limited territories along the transverse axis of both muscles must be assumed in order to explain why most MUs act on all tendons and why force distributions change with increasing stimulus frequency. In addition, specific relations between unit type and force distributions were found within both muscles. Fatigue-resistant EDC MUs have broader force distributions than fatigue-sensitive EDC MUs and slow ECU MUs were found to act predominantly on the most ulnar part of the distal tendon. These biomechanical properties of MUs are discussed as supporting the specific functions of the respective muscles.

Recovery of motor-unit function after peripheral nerve injury in aged rats

The potential capacity of aged motoneurons for the reconstruction of motor-units after nerve crush injury was studied in the medial gastrocnemius (MG) muscle of male Fischer rats. The MG nerve in middle-aged (8 months old) and aged (24 months) rats was aseptically crushed under pentobarbital anesthesia. After a 3-month recovery period, the animal was reanesthetized and physiological properties of individual motor-units were recorded. The three different types (fast twitch, fatigable: FF; fast twitch, fatigue resistant: FR and slow twitch: S) of normal motor-unit organization were restored in both middle-aged and aged reinnervated muscles as measured by their relative distributions, mean twitch contraction times and mean tetanic tensions. Some reinnervated units in both aged and middle-aged rats produced a large tetanic tension which exceeded the range for intact units. These findings indicate that aged motoneurons maintain their ability for axonal regenerating and muscle fiber innervation to reestablish normal function of motor-units.

Organization of motor units in the axolotl: A continuously growing animal

The characteristics of motor units in the iliotibialis posterior muscle of the axolotl hindlimb are described. Tension recording and intracellular electrophysiological methods demonstrate that the physiological properties of the population of motor units are continuously distributed rather than grouped into a series of discrete types. Overlap between motor units occurs and this is positively correlated with motor unit size but negatively correlated with differences in time to peak tension. Immunocytochemical staining with antimyosin antibodies combined with histochemical demonstration of actomyosin ATPase activity revealed at least four types of muscle fibre which were distributed asymmetrically within iliotibialis posterior. The results are discussed in terms of the continuous growth of the muscle and the interactions between muscle and nerve in the formation of the axolotl motor system.