Enhanced motor unit rate coding with improvements in a force-matching task

These data describe improved modulation of discharge rates (rate coding) of first dorsal interosseous motor units throughout the acquisition of a complex force-matching skill involving isometric index finger abduction. In each of 15 consecutive trials, subjects attempted to match their force to a trajectory consisting of the sum of two sine waves (0.15 and 0.5 Hz) and random oscillations (overall mean force level ˜20% MVC). Reductions in root-mean-square (RMS) error of each subject’s force relative to the trajectory indicated substantial improvements in force-matching ability (F=33.8, p<0.001). With the acquisition of this new skill, there was increased amplitude modulation of muscular force near both dominant frequencies of the force-matching trajectory (F=10.6, p=0.008). The standard deviation and coefficient of variation of motor unit inter-spike intervals both decreased with improved performance indicating a general reduction in the amplitude of firing rate modulations (SD: F=18.69, p=0.001; CV: F=43.6, p<0.001). After skill acquisition, there was decreased firing rate modulation outside of the two dominant frequencies and increased amplitude of firing rate modulation at the higher of the two dominant frequencies (0.5 Hz, F=8.23, p=0.015). These findings indicate that improved precision of rate coding was a contributor to the acquisition of the new force-matching task. That the change in rate coding was frequency dependent suggests that factors other than frequency coding may contribute to the improved force matching at 0.15 Hz.     

Mesodermal and neuronal retinoids regulate the induction and maintenance of limb innervating spinal motor neurons

During embryonic development, the generation, diversification and maintenance of spinal motor neurons depend upon extrinsic signals that are tightly regulated. Retinoic acid (RA) is necessary for specifying the fates of forelimb-innervating motor neurons of the Lateral Motor Column (LMC), and the specification of LMC neurons into medial and lateral subtypes. Previous studies implicate motor neurons as the relevant source of RA for specifying lateral LMC fates at forelimb levels. However, at the time of LMC diversification, a significant amount of retinoids in the spinal cord originates from the adjacent paraxial mesoderm. Here we employ mouse genetics to show that RA derived from the paraxial mesoderm is required for lateral LMC induction at forelimb and hindlimb levels, demonstrating that mesodermally synthesized RA functions as a second source of signals to specify lateral LMC identity. Furthermore, reduced RA levels in postmitotic motor neurons result in a decrease of medial and lateral LMC neurons, and abnormal axonal projections in the limb; invoking additional roles for neuronally synthesized RA in motor neuron maintenance and survival. These findings suggest that during embryogenesis, mesodermal and neuronal retinoids act coordinately to establish and maintain appropriate cohorts of spinal motor neurons that innervate target muscles in the limb.     

The Legs at odd angles (Loa) Mutation in Cytoplasmic Dynein Ameliorates Mitochondrial Function in SOD1G93A Mouse Model for Motor Neuron Disease

Amyotrophic lateral sclerosis (ALS) is a debilitating and fatal late-onset neurodegenerative disease. Familial cases of ALS (FALS) constitute ∼10% of all ALS cases, and mutant superoxide dismutase 1 (SOD1) is found in 15–20% of FALS. SOD1 mutations confer a toxic gain of unknown function to the protein that specifically targets the motor neurons in the cortex and the spinal cord. We have previously shown that the autosomal dominant Legs at odd angles (Loa) mutation in cytoplasmic dynein heavy chain (Dync1h1) delays disease onset and extends the life span of transgenic mice harboring human mutant SOD1^G93A. In this study we provide evidence that despite the lack of direct interactions between mutant SOD1 and either mutant or wild-type cytoplasmic dynein, the Loa mutation confers significant reductions in the amount of mutant SOD1 protein in the mitochondrial matrix. Moreover, we show that the Loa mutation ameliorates defects in mitochondrial respiration and membrane potential observed in SOD1^G93A motor neuron mitochondria. These data suggest that the Loa mutation reduces the vulnerability of mitochondria to the toxic effects of mutant SOD1, leading to improved mitochondrial function in SOD1^G93A motor neurons.     

Trunk control during repetitive sagittal movements following a real-time tracking task in people with chronic low back pain

Precision of trunk movement has commonly been examined by testing relocation accuracy rather than evaluating accuracy of tracking dynamic movement. In this study we used a 3-D motion capture system to provide a novel real-time tracking task to assess trunk motor control at varying movement speeds between people with and without chronic non-specific low back pain (LBP). Eleven asymptomatic volunteers and 15 participants with chronic non-specific LBP performed 12 continuous cycles of trunk flexion–extension following real time visual feedback, during which, trunk motion was measured using eight optoelectronic infrared cameras. Significant time differences between the feedback and actual trunk motion were found between groups (P = 0.001). Both groups had similar variability of tracking accuracy when following the feedback (P > 0.05). However, tracking variability at a slow speed correlated (P = 0.03; r = 0.55) with the Fear-Avoidance Beliefs Questionnaire (FABQ) scores in those with LBP. This study shows that both asymptomatic people and individuals with LBP displayed anticipatory behaviour, however, the response of those with LBP was consistently delayed in tracking the visual feedback compared to the asymptomatic group. Additionally, the extent of variability of tracking accuracy over repeated tracking cycles was associated with the degree of fear of movement in people with LBP.     

Consensus for experimental design in electromyography (CEDE) project: Single motor unit matrix

The analysis of single motor unit (SMU) activity provides the foundation from which information about the neural strategies underlying the control of muscle force can be identified, due to the one-to-one association between the action potentials generated by an alpha motor neuron and those received by the innervated muscle fibers. Such a powerful assessment has been conventionally performed with invasive electrodes (i.e., intramuscular electromyography (EMG)), however, recent advances in signal processing techniques have enabled the identification of single motor unit (SMU) activity in high-density surface electromyography (HDsEMG) recordings. This matrix, developed by the Consensus for Experimental Design in Electromyography (CEDE) project, provides recommendations for the recording and analysis of SMU activity with both invasive (needle and fine-wire EMG) and non-invasive (HDsEMG) SMU identification methods, summarizing their advantages and disadvantages when used during different testing conditions. Recommendations for the analysis and reporting of discharge rate and peripheral (i.e., muscle fiber conduction velocity) SMU properties are also provided. The results of the Delphi process to reach consensus are contained in an appendix. This matrix is intended to help researchers to collect, report, and interpret SMU data in the context of both research and clinical applications.     

Developmental Expression of the Outer Hair Cell Motor Prestin in the Mouse

The development of motor protein activity in the lateral membrane of the mouse outer hair cell (OHC) from postnatal day 5 (P5) to P18 was investigated under whole-cell voltage clamp. Voltage-dependent, nonlinear capacitance (C _v), which represents the conformational fluctuations of the motor molecule, progressively increased during development. At P12, the onset of hearing in the mouse, C _v was about 70% of the mature level. C _v saturated at P18 when hearing shows full maturation. On the other hand, C _lin, which represents the membrane area of the OHC, showed a relatively small increase with development, reaching steady state at P10. This early maturation of linear capacitance is further supported by morphological estimates of surface area during development. These results, in light of recent prestin knockout experiments and our results with quantitative polymerase chain reaction, suggest that, rather than the incorporation of new motors into the lateral membrane after P10, molecular motors mature to augment nonlinear capacitance. Thus, current estimates of motor protein density based on charge movement may be exaggerated. A corresponding indicator of motor maturation, the motor’s operating voltage midpoint, V _pkcm, tended to shift to depolarized potentials during postnatal development, although it was unstable prior to P10. However, after P14, V _pkcm reached a steady-state level near −67 mV, suggesting that intrinsic membrane tension or intracellular chloride, each of which can modulate V _pkcm, may mature at P14. These developmental data significantly alter our understanding of the cellular mechanisms that control cochlear amplification and provide a foundation for future analysis of genetic modifications of mouse auditory development.     

Abdominal muscle activation changes if the purpose is to control pelvis motion or thorax motion

The aim of this study was to compare trunk muscular recruitment and lumbar spine kinematics when motion was constrained to either the thorax or the pelvis. Nine healthy women performed four upright standing planar movements (rotations, anterior–posterior translations, medial–lateral translations, and horizontal circles) while constraining pelvis motion and moving the thorax or moving the pelvis while minimizing thorax motion, and four isometric trunk exercises (conventional curl-up, reverse curl-up, cross curl-up, and reverse cross curl-up). Surface EMG (upper and lower rectus abdominis, lateral and medial aspects of external oblique, internal oblique, and latissimus dorsi) and 3D lumbar displacements were recorded. Pelvis movements produced higher EMG amplitudes of the oblique abdominals than thorax motions in most trials, and larger lumbar displacements in the medial–lateral translations and horizontal circles. Conversely, thorax movements produced larger rotational lumbar displacement than pelvis motions during rotations and higher EMG amplitudes for latissimus dorsi during rotations and anterior–posterior translations and for lower rectus abdominis during the crossed curl-ups. Thus, different neuromuscular compartments appear when the objective changes from pelvis to thorax motion. This would suggest that both movement patterns should be considered when planning spine stabilization programs, to optimize exercises for the movement and muscle activations desired.     

AMaCAID: a useful tool for Accurate Marker Choice for Accession Identification and Discrimination

AMaCAID is an R program designed to analyse multilocus genotypic patterns in large samples. It allows (i) the computation of the number and frequency of the different multilocus patterns available in a molecular data set and (ii) the analysis of discriminatory power of each combination of k markers among n available. It thus enables the identification of the minimum number of markers required to distinguish all the observed genotypes and the subset of markers that maximize the number of distinct genotypes. AMaCAID can be used with any kind of molecular markers, on data sets mixing different kinds of markers, but also on qualitative characters like morphological or taxonomic traits. AMaCAID has been built primarily to select subsets of markers for identifying accessions and monitoring their genetic stability during regeneration cycles in an ex situ genebank. It can, however, also be used to screen any kind of data set that characterizes a set of individuals or species (e.g. taxonomic or phylogenetic studies) for discrimination purposes. The size of the assayed sample has no limitation, but the program only performs computations on all combinations of markers when there are less than 25 markers. For larger number of markers/characters, it is possible to ask AMaCAID to screen a large but limited number of combinations of markers. We apply AMaCAID to three data sets involving either molecular or taxonomic data and give some results on the computing time of the program with respect to the size of the data set.