Motoneuron Activity Research Articles

Enhancement of time-frequency energy for the classification of motor imagery electroencephalogram based on an improved FitzHugh-Nagumo neuron system.

Brain-computer interface (BCI) based on motor imagery (MI) electroencephalogram (EEG) has become an essential way for rehabilitation, because of the activation and interaction of motor neurons between the brain and rehabilitation devices in recent years. However, due to the discrepancies between individuals, the frequency ranges can be different even for the same rhythm component of EEG recordings, which brings difficulties to the extraction of features for MI classification. Typical algorithms for MI classification such as common spatial patterns (CSP) require multi-channel analysis and lack frequency information. With the development of BCI, the single-channel BCI system has become indispensable for simplicity of use. However, the currently available single-channel detection methods have low classification accuracy. To address this issue, two novel frameworks based on an improved two-dimensional nonlinear FitzHugh-Nagumo (FHN) neuron system are proposed to extract features of the single-channel MI. To evaluate the effectiveness of the proposed methods, this research utilized an open-access database (BCI competition IV dataset 2a), an offline database, and a 10-fold cross-validation procedure. Experimental results showed that the improved nonlinear FHN system can transfer the energy of noise into MI, thereby effectively enhancing the time-frequency energy. Compared with the traditional methods, the proposed methods can achieve higher classification accuracy and robustness.

Mapping Individual Motor Unit Activity to Continuous Three-DoF Wrist Torques: Perspectives for Myoelectric Control.

The surface electromyography (EMG) decomposition techniques provide access to motor neuron activities and have been applied to myoelectric control schemes. However, the current decomposition-based myoelectric control mainly focuses on discrete gestures or single-DoF continuous movements. In this study, we aimed to map the motor unit discharges, which were identified from high-density surface EMG, to the three degrees of freedom (DoFs) wrist movements. The 3-DoF wrist torques and high-density surface EMG signals were recorded concurrently from eight non-disabled subjects. The experimental protocol included single-DoF movements and their various combinations. We decoded the motor unit discharges from the EMG signals using a segment-wise decomposition algorithm. Then the neural features were extracted from motor unit discharges and projected to wrist torques with a multiple linear regression model. We compared the performance of two neural features (twitch model and spike counting) and two training schemes (single-DoF and multi-DoF training). On average, 145 ± 33 motor units were identified from each subject, with a pulse-to-noise ratio of 30.8 ± 4.2 dB. Both neural features exhibited high estimation accuracy of 3-DoF wrist torques, with an average [Formula: see text] of 0.76 ± 0.12 and normalized root mean square error of 11.4 ± 3.1%. These results demonstrated the efficiency of the proposed method in continuous estimation of 3-DoF wrist torques, which has the potential to advance dexterous myoelectric control based on neural information.

In vivo optogenetic inhibition of striatal parvalbumin-reactive interneurons induced genotype-specific changes in neuronal activity without dystonic signs in male DYT1 knock-in mice.

The pathophysiology of early-onset torsion dystonia (TOR1A/DYT1) remains unclear. Like 70% of human mutation carriers, rodent models with ΔGAG mutation such as DYT1 knock-in (KI) mice do not show overt dystonia but have subtle sensorimotor deficits and pattern of abnormal synaptic plasticity within the striatal microcircuits. There is evidence that dysfunction of striatal parvalbumin-reactive (Parv+) fast-spiking interneurons (FSIs) can be involved in dystonic signs. To elucidate the relevance of these GABAergic interneurons in the pathophysiology of DYT1 dystonia, we used in vivo optogenetics to specifically inhibit Parv+ and to detect changes in motor behavior and neuronal activity. Optogenetic fibers were bilaterally implanted into the dorsal striatum of male DYT1 KI mice and wild-type (WT) littermates expressing halorhodopsin (eNpHR3.0) in Parv+ interneurons. While stimulations with yellow light pulses for up to 60 min at different pulse durations and interval lengths did not induce abnormal movements, such as dystonic signs, immunohistochemical examinations revealed genotype-dependent differences. In contrast to WT mice, stimulated DYT1 KI showed decreased striatal neuronal activity, that is, less c-Fos reactive neurons, and increased activation of cholinergic interneurons after optogenetic inhibition of Parv+ interneurons. These findings suggest an involvement of Parv+ interneurons in an impaired striatal network in DYT1 KI mice, but at least short-term inhibition of these GABAergic interneurons is not sufficient to trigger a dystonic phenotype, similar to previously shown optogenetic activation of cholinergic interneurons.

Inhibition by rno-circRNA-013017 of the apoptosis of motor neurons in anterior horn and descending axonal degeneration in rats after traumatic spinal cord injury.

Spinal cord injury (SCI) often causes continuous neurological damage to clinical patients. Circular RNAs (circRNAs) are related to a lot of diseases, including SCI. We previously found five candidate circRNAs which were likely to regulate the secondary pathophysiological changes in rat model after traumatic SCI. In this study, we first selected and overexpressed target circRNA in rats. We then explored its functional roles using various functional assays in a rat model after SCI. We found that rno-circRNA-013017-the selected target circRNA-reduced neuron apoptosis, preserved the survival and activity of motor neurons, and regulated apoptosis-related proteins at 3 days post-SCI using western blot, immunofluorescence and polymerase chain reaction. Additionally, we found that rno-circRNA-013017 inhibited descending axonal degeneration and preserved motor neurons and descending axons at 6 weeks post-SCI using immunofluorescence, biotin dextran amine diffusion tensor imaging. Finally, the overexpression of rno-circRNA-013017 promoted the locomotor function of rats after SCI using open-field test and gait analysis. Focusing on the functions of rno-circRNA-013017, this study provides new options for future studies exploring therapeutic targets and molecular mechanisms for SCI.

Spinal premotor interneurons controlling antagonistic muscles are spatially intermingled.

Elaborate behaviours are produced by tightly controlled flexor-extensor motor neuron activation patterns. Motor neurons are regulated by a network of interneurons within the spinal cord, but the computational processes involved in motor control are not fully understood. The neuroanatomical arrangement of motor and premotor neurons into topographic patterns related to their controlled muscles is thought to facilitate how information is processed by spinal circuits. Rabies retrograde monosynaptic tracing has been used to label premotor interneurons innervating specific motor neuron pools, with previous studies reporting topographic mediolateral positional biases in flexor and extensor premotor interneurons. To more precisely define how premotor interneurons contacting specific motor pools are organized, we used multiple complementary viral-tracing approaches in mice to minimize systematic biases associated with each method. Contrary to expectations, we found that premotor interneurons contacting motor pools controlling flexion and extension of the ankle are highly intermingled rather than segregated into specific domains like motor neurons. Thus, premotor spinal neurons controlling different muscles process motor instructions in the absence of clear spatial patterns among the flexor-extensor circuit components.

A Prediction of Fingertip Force and Joint Kinematics of Individual Fingers using Motoneuron Firing Activities

<h3>Research Objectives</h3> Advanced assistive robotic hands can help individuals with hand impairment to perform daily activities. The detection of intended motor output of individual fingers, however, remains a challenge. The objective of this study was to develop a decoding method to continuously and simultaneously predict fingertip forces and joint kinematics of individual fingers using motoneuron firing frequency. <h3>Design</h3> Blind source separation method was applied to EMG signals to obtain motor unit (MU) firing activities. MU refinement procedure was used to determine finger- and task-specific MU pools. Obtained MU pools were tested on different datasets involving both isometric and dynamic tasks (combined). Populational MU firing frequencies were calculated to estimate the fingertip forces and joint angles concurrently using regression models. Model performance was compared with conventional EMG amplitude-based approach. <h3>Setting</h3> The study was carried out at the NC State/UNC Joint Department of Biomedical Engineering. <h3>Participants</h3> Seven healthy volunteers (Age: 28±7) participated in this study. No participant had any prior neuro-muscular ailments. All participants provided an informed consent. <h3>Interventions</h3> Not applicable. <h3>Main Outcome Measure(s)</h3> Concurrent and continuous prediction of finger kinetics and kinematics via motoneuron activities. <h3>Results</h3> MU approach led to better performance (higher correlation between the predicted and measured output and lower prediction error) in predicting both joint angles and fingertip forces than the EMG amplitude approach. <h3>Conclusion(s)</h3> MU pools can be identified for specific finger-task combinations, which allows concurrent control of fingertip forces and joint angles with assistive robot hands. Separation matrix derived from single finger trials was used applied to combined trials to avoid the computationally intensive nature of HD-EMG decomposition and to determine its usability in real-time. Further development of this method could provide concurrent and continuous control of individual finger movements of highly dexterous robotic hands.

Acute Intermittent Hypoxia Increases Motor Unit Discharge Rates And Strength in Persons with SCI

<h3>Research Objectives</h3> To determine whether changes in motor unit discharge rates contribute to acute intermittent hypoxia (AIH)-induced improvements in volitional strength in persons with chronic incomplete spinal cord injury (iSCI) at the cervical level. <h3>Design</h3> Repeated-measures crossover study. <h3>Setting</h3> Rehabilitation hospital. <h3>Participants</h3> Seven individuals with iSCI completed two different sessions (AIH and SHAM) in a randomized order. <h3>Interventions</h3> AIH consisted of breathing 15 brief (∼60s) periods of low oxygen (9% O2) interspersed with 60s of normoxia (21% O2), whereas SHAM consisted of repeated exposures to normoxia. <h3>Main Outcome Measures</h3> We recorded high-density surface electromyograms from biceps and triceps brachii during maximal elbow flexion and extension torques, and decomposed these signals into individual motor unit spike trains before and 60 minutes after the interventions. <h3>Results</h3> After AIH, elbow flexion and extension torque increased by 54% (p = 0.0078; g = 0.58) and 59% (p = 0.04, g = 0.63) from baseline, respectively, whereas there was no change (i.e. < 10% change and p > 0.2 in both cases) after SHAM. Across muscles, motor unit discharge rates increased by 3.96 pulses per second (∼38%; p = 0.0015; G = 0.86) during maximal efforts, from pre to post AIH. Using generalized linear mixed models, we found that changes in motor unit discharge rates explained 54% (p = 0.0033) of the variance of changes in volitional torque. <h3>Conclusions</h3> These findings suggest that excitability and/or the activation of spinal motoneurons are augmented after AIH, providing a mechanism to explain AIH-induced increases in voluntary strength. Pending validation, AIH could potentially be used in conjunction with other therapies to enhance rehabilitation outcomes due to these enhancements in motor unit function and strength. <h3>Author(s) Disclosures</h3> The authors have nothing to disclose.

The elusive cephalic phase insulin response: triggers, mechanisms, and functions.

The cephalic phase insulin response (CPIR) is classically defined as a head receptor-induced early release of insulin during eating that precedes a postabsorptive rise in blood glucose. Here we discuss, first, the various stimuli that elicit the CPIR and the sensory signaling pathways (sensory limb) involved; second, the efferent pathways that control the various endocrine events associated with eating (motor limb); and third, what is known about the central integrative processes linking the sensory and motor limbs. Fourth, in doing so, we identify open questions and problems with respect to the CPIR in general. Specifically, we consider test conditions that allow, or may not allow, the stimulus to reach the potentially relevant taste receptors and to trigger a CPIR. The possible significance of sweetness and palatability as crucial stimulus features and whether conditioning plays a role in the CPIR are also discussed. Moreover, we ponder the utility of the strict classical CPIR definition based on what is known about the effects of vagal motor neuron activation and thereby acetylcholine on the β-cells, together with the difficulties of the accurate assessment of insulin release. Finally, we weigh the evidence of the physiological and clinical relevance of the cephalic contribution to the release of insulin that occurs during and after a meal. These points are critical for the interpretation of the existing data, and they support a sharper focus on the role of head receptors in the overall insulin response to eating rather than relying solely on the classical CPIR definition.

Blind identification of the spinal cord output in humans with high-density electrode arrays implanted in muscles.

Invasive electromyography opened a new window to explore motoneuron behavior in vivo. However, the technique is limited by the small fraction of active motoneurons that can be concurrently detected, precluding a population analysis in natural tasks. Here, we developed a high-density intramuscular electrode for in vivo human recordings along with a fully automatic methodology that could detect the discharges of action potentials of up to 67 concurrently active motoneurons with 99% accuracy. These data revealed that motoneurons of the same pool receive common synaptic input at frequencies up to 75 Hz and that late-recruited motoneurons inhibit the discharges of those recruited earlier. These results constitute an important step in the population coding analysis of the human motor system in vivo.

Fmrp regulates neuronal balance in embryonic motor circuit formation.

Motor behavior requires the balanced production and integration of a variety of neural cell types. Motor neurons are positioned in discrete locations in the spinal cord, targeting specific muscles to drive locomotive contractions. Specialized spinal interneurons modulate and synchronize motor neuron activity to achieve coordinated motor output. Changes in the ratios and connectivity of spinal interneurons could drastically alter motor output by tipping the balance of inhibition and excitation onto target motor neurons. Importantly, individuals with Fragile X syndrome (FXS) and associated autism spectrum disorders often have significant motor challenges, including repetitive behaviors and epilepsy. FXS stems from the transcriptional silencing of the gene Fragile X Messenger Ribonucleoprotein 1 (FMR1), which encodes an RNA binding protein that is implicated in a multitude of crucial neurodevelopmental processes, including cell specification. Our work shows that Fmrp regulates the formation of specific interneurons and motor neurons that comprise early embryonic motor circuits. We find that zebrafish fmr1 mutants generate surplus ventral lateral descending (VeLD) interneurons, an early-born cell derived from the motor neuron progenitor domain (pMN). As VeLD interneurons are hypothesized to act as central pattern generators driving the earliest spontaneous movements, this imbalance could influence the formation and long-term function of motor circuits driving locomotion. fmr1 embryos also show reduced expression of proteins associated with inhibitory synapses, including the presynaptic transporter vGAT and the postsynaptic scaffold Gephyrin. Taken together, we show changes in embryonic motor circuit formation in fmr1 mutants that could underlie persistent hyperexcitability.

Beta inputs to motor neurons do not directly contribute to volitional force modulation.

Neural oscillatory activity in the beta band (13-30Hz) is prominent in the brain and it is transmitted partly linearly to the spinal cord and muscles. Multiple views on the functional relevance of beta activity in the motor system have been proposed. Previous simulation work suggested that pools of spinal motoneurons (MNs) receiving a common beta input could demodulate this activity, transforming it into low-frequency neural drive that could alter force production in muscles. This may suggest that common beta inputs to muscles have a direct role in force modulation. Here we report the experimental average levels and ranges of common beta activity in spinal MNs projecting to single muscles and use a computational model of a MN pool to test if the experimentally observed beta levels in MNs can influence force. When beta was modelled as a continuous activity, the amplitude needed to produce non-negligible changes in force corresponded to beta representation in the MN pool that was far above the experimental observations. On the other hand, when beta activity was modelled as short-lived events (i.e. bursts of beta activity separated by intervals without beta oscillations), this activity approximated levels that could cause small changes in force with estimated average common beta inputs to the MNs compatible with the experimental observations. Nonetheless, bursting beta is unlikely to be used for force control due to the temporal sparsity of this activity. It is therefore concluded that beta oscillations are unlikely to contribute to the voluntary modulation of force. KEY POINTS: It has been previously proposed that beta (13-30Hz) common inputs to a motor neuron pool may have a non-linear effect in voluntary force control. The needed strength of beta oscillations to modulate forces has not been analysed yet. Based on computer simulations, we show that sustained beta inputs to a spinal motoneuron pool at physiologically reported levels have minimal effect on force. Levels of sustained beta rhythmic activity that can cause a significant change in force are not compatible with experimental observations of intramuscular coherence in human skeletal muscles.

Assessment of trunk control and core stability in spinal cord injured subjects

Objective measures for evaluating active trunk movements and postural control in sitting are important for the assessment of people with Spinal Cord Injury (SCI) and for tailoring rehabilitative interventions. However, studies addressing this issue are limited [1]. This work fills this gap by proposing a modular protocol for the kinematic and muscular quantitative assessment of trunk control, specifically designed for SCI subjects. We used hunova® (Movendo Technology), a medical robotic device for the sensory-motor assessment and training of postural control in standing and sitting [2]. consisted of two different tests: a reaching (R) and an adaptive exercise (A), both performed while sitting on hunova®. The test R aims to assess the volitional component of trunk control: six reaching exercises, where subjects need to actively tilt the seat platform to move a cursor on the screen and reach targets, are alternating with two different platform inclinations: 3.5 and 5° (1° corresponds to 1 cm of cursor motion on the screen). The test A aims to assess how subjects adapt to predictable perturbations imposed by the seat platform [3]: six repetitions of an adaptive task, where subjects need to stabilize themselves while the seat platform moves following a given infinite-shape trajectory, is repeated once with eyes open (EO) and eyes close (EC), with different inclinations of the seat platform: 3, 5 and 7°. After testing the device and protocol on 18 healthy subjects, 10 SCI subjects (with different lesion level) participated in the study. Both the reaching block and the adaptive block (Fig. 1) started with the easiest testing condition and gradually increases the difficulty of the exercises. This allowed all SCI subjects, with different lesion level, to participate in the assessment. Electromyography (EMG) was recorded bilaterally from the following muscles: obliquus externus abdominis, trapezius descendens, trapezius transversalis, trapezius ascendens, erector spinae longissimus, erector spinae iliocostalis, multifidus, latissimus dorsi, soleus, tibialis anterior, vastus medialis, semitendinosus, gluteus medium. The leg muscles were recorded only for SCI subjects with an incomplete lesion of the spinal cord. For each subject, we characterized postural responses in terms of kinematics and muscular activity, estimating the correspondent spatiotemporal organization of the motoneuronal activity in the spinal cord [4]. All subjects with an incomplete SCI could finish the whole protocol. This was not the case for subjects with a complete lesion. Only one subject (lesion level D12) completed both blocks and had movement performance like SCI subjects with an incomplete lesion. The other subjects (two with lesion level D6 and one D3) performed few repetitions of R as they found difficult to control the seat platform, and the tasks with 3 and 5° of inclination for A. Concerning the performance, for R all subjects, independently on their type of lesion, reached a greater number of targets across repetitions. During A, all subjects had a bigger trunk sway for higher inclinations of the seat platform, with higher values in the repetitions with EC. Each SCI subject used his/her own muscular strategy for reaching the different targets and also for adapting to the seat motion, despite it was continuous and predictable. This assessment highlighted the differences in the muscular control among subjects, also due to the different lesions. This modular protocol evaluated in a quantitative, objective, repeatable, and comprehensive manner the kinematic and muscular strategies adopted by SCI subjects when performing dynamic tasks while sitting. The device hunova® allowed us to evaluate different aspects related to trunk control, the volitional and the feedforward control of balance while adapting to predictable and continuous perturbations. The results of this assessment will be used to tailor specific rehabilitative interventions.

Extrasynaptic signaling enables an asymmetric juvenile motor circuit to produce symmetric undulation

In many animals, there is a direct correspondence between the motor patterns that drive locomotion and the motor neuron innervation. For example, the adult C.elegans moves with symmetric and alternating dorsal-ventral bending waves arising from symmetric motor neuron input onto the dorsal and ventral muscles. In contrast to the adult, the C.elegans motor circuit at the juvenile larval stage has asymmetric wiring between motor neurons and muscles but still generates adult-like bending waves with dorsal-ventral symmetry. We show that in the juvenile circuit, wiring between excitatory and inhibitory motor neurons coordinates the contraction of dorsal muscles with relaxation of ventral muscles, producing dorsal bends. However, ventral bending is not driven by analogous wiring. Instead, ventral muscles are excited uniformly by premotor interneurons through extrasynaptic signaling. Ventral bends occur in anti-phasic entrainment to activity of the same motor neurons that drive dorsal bends. During maturation, the juvenile motor circuit is replaced by two motor subcircuits that separately drive dorsal and ventral bending. Modeling reveals that the juvenile's immature motor circuit is an adequate solution to generate adult-like dorsal-ventral bending before the animal matures. Developmental rewiring between functionally degenerate circuit solutions, which both generate symmetric bending patterns, minimizes behavioral disruption across maturation.

Calcium transients in intramuscular interstitial cells of Cajal of the murine gastric fundus and their regulation by neuroeffector transmission.

Enteric neurotransmission is critical for coordinating motility throughout the gastrointestinal (GI) tract. However, there is considerable controversy regarding the cells that are responsible for the transduction of these neural inputs. In the present study, utilization of a cell-specific calcium biosensor GCaMP6f, the spontaneous activity and neuroeffector responses of intramuscular ICC (ICC-IM) to motor neural inputs was examined. Simultaneous intracellular microelectrode recordings and high-speed video-imaging during nerve stimulation was used to reveal the temporal relationship between changes in intracellular Ca2+ and post-junctional electrical responses to neural stimulation. ICC-IM were highly active, generating intracellular Ca2+ -transients that occurred stochastically, from multiple independent sites in single ICC-IM. Ca2+ -transients were not entrained in single ICC-IM or between neighbouring ICC-IM. Activation of enteric motor neurons produced a dominant inhibitory response that abolished Ca2+ -transients in ICC-IM. This inhibitory response was often preceded by a summation of Ca2+ -transients that led to a global rise in Ca2+ . Individual ICC-IM responded to nerve stimulation by a global rise in Ca2+ followed by inhibition of Ca2+ -transients. The inhibition of Ca2+ -transients was blocked by the nitric oxide synthase antagonist l-NNA. The global rise in intracellular Ca2+ was inhibited by the muscarinic antagonist, atropine. Simultaneous intracellular microelectrode recordings with video-imaging revealed that the rise in Ca2+ was temporally associated with rapid excitatory junction potentials and the inhibition of Ca2+ -transients with inhibitory junction potentials. These data support the premise of serial innervation of ICC-IM in excitatory and inhibitory neuroeffector transmission in the proximal stomach. KEY POINTS: The cells responsible for mediating enteric neuroeffector transmission remain controversial. In the stomach intramuscular interstitial cells of Cajal (ICC-IM) were the first ICC reported to receive cholinergic and nitrergic neural inputs. Utilization of a cell specific calcium biosensor, GCaMP6f, the activity, and neuroeffector responses of ICC-IM were examined. ICC-IM were highly active, generating stochastic intracellular Ca2+ -transients. Stimulation of enteric motor nerves abolished Ca2+ -transients in ICC-IM. This inhibitory response was preceded by a global rise in intracellular Ca2+ . Individual ICC-IM responded to nerve stimulation with a rise in Ca2+ followed by inhibition of Ca2+ -transients. Inhibition of Ca2+ -transients was blocked by the nitric oxide synthase antagonist l-NNA. The global rise in Ca2+ was inhibited by the muscarinic antagonist atropine. Simultaneous intracellular recordings with video imaging revealed that the global rise in intracellular Ca2+ and inhibition of Ca2+ -transients was temporally associated with rapid excitatory junction potentials followed by more sustained inhibitory junction potentials. The data presented support the premise of serial innervation of ICC-IM in excitatory and inhibitory neuroeffector transmission in the proximal stomach.

Cholinergic Modulation of Locomotor Circuits in Vertebrates.

Locomotion is a basic motor act essential for survival. Amongst other things, it allows animals to move in their environment to seek food, escape predators, or seek mates for reproduction. The neural mechanisms involved in the control of locomotion have been examined in many vertebrate species and a clearer picture is progressively emerging. The basic muscle synergies responsible for propulsion are generated by neural networks located in the spinal cord. In turn, descending supraspinal inputs are responsible for starting, maintaining, and stopping locomotion as well as for steering and controlling speed. Several neurotransmitter systems play a crucial role in modulating the neural activity during locomotion. For instance, cholinergic inputs act both at the spinal and supraspinal levels and the underlying mechanisms are the focus of the present review. Much information gained on supraspinal cholinergic modulation of locomotion was obtained from the lamprey model. Nicotinic cholinergic inputs increase the level of excitation of brainstem descending command neurons, the reticulospinal neurons (RSNs), whereas muscarinic inputs activate a select group of hindbrain neurons that project to the RSNs to boost their level of excitation. Muscarinic inputs also reduce the transmission of sensory inputs in the brainstem, a phenomenon that could help in sustaining goal directed locomotion. In the spinal cord, intrinsic cholinergic inputs strongly modulate the activity of interneurons and motoneurons to control the locomotor output. Altogether, the present review underlines the importance of the cholinergic inputs in the modulation of locomotor activity in vertebrates.

Chemogenetic activation of hypoglossal motoneurons in a mouse model of Pompe disease.

Pompe disease is a lysosomal storage disease resulting from absence or deficiency of acid α-glucosidase (GAA). Tongue-related disorders including dysarthria, dysphagia, and obstructive sleep apnea are common in Pompe disease. Our purpose was to determine if designer receptors exclusively activated by designer drugs (DREADDs) could be used to stimulate tongue motor output in a mouse model of Pompe disease. An adeno-associated virus serotype 9 (AAV9) encoding an excitatory DREADD (AAV9-hSyn-hM3D(Gq)-mCherry, 2.44 × 1010 vg) was administered to the posterior tongue of 5-7-wk-old Gaa null (Gaa-/-) mice. Lingual EMG responses to intraperitoneal injection of saline or a DREADD ligand (JHU37160-dihydrochloride, J60) were assessed 12 wk later during spontaneous breathing. Saline injection produced no consistent changes in lingual EMG. Following the DREADD ligand, there were statistically significant (P < 0.05) increases in both tonic and phasic inspiratory EMG activity recorded from the posterior tongue. Brainstem histology confirmed mCherry expression in hypoglossal (XII) motoneurons in all mice, thus verifying retrograde movement of the AAV9 vector. Morphologically, Gaa-/- XII motoneurons showed histological characteristics that are typical of Pompe disease, including an enlarged soma and vacuolization. We conclude that lingual delivery of AAV9 can be used to drive functional expression of DREADD in XII motoneurons in a mouse model of Pompe disease.NEW & NOTEWORTHY In a mouse model of Pompe disease, lingual injection of adeno-associated virus (AAV) serotype 9 encoding DREADD was histologically verified to produce transgene expression in hypoglossal motoneurons. Subsequent intraperitoneal delivery of a DREADD ligand stimulated tonic and phase tongue motor output.In a mouse model of Pompe disease, lingual injection of adeno-associated virus (AAV) serotype 9 encoding DREADD was histologically verified to produce transgene expression in hypoglossal motoneurons. Subsequent intravenous delivery of a DREADD ligand stimulated tonic and phase tongue motor output.

Evaluation of Spatiotemporal Patterns of the Spinal Muscle Coordination Output during Walking in the Exoskeleton.

Recent advances in the performance and evaluation of walking in exoskeletons use various assessments based on kinematic/kinetic measurements. While such variables provide general characteristics of gait performance, only limited conclusions can be made about the neural control strategies. Moreover, some kinematic or kinetic parameters are a consequence of the control implemented on the exoskeleton. Therefore, standard indicators based on kinematic variables have limitations and need to be complemented by performance measures of muscle coordination and control strategy. Knowledge about what happens at the spinal cord output level might also be critical for rehabilitation since an abnormal spatiotemporal integration of activity in specific spinal segments may result in a risk for abnormalities in gait recovery. Here we present the PEPATO software, which is a benchmarking solution to assess changes in the spinal locomotor output during walking in the exoskeleton with respect to reference data on normal walking. In particular, functional and structural changes at the spinal cord level can be mapped into muscle synergies and spinal maps of motoneuron activity. A user-friendly software interface guides the user through several data processing steps leading to a set of performance indicators as output. We present an example of the usage of this software for evaluating walking in an unloading exoskeleton that allows a person to step in simulated reduced (the Moon’s) gravity. By analyzing the EMG activity from lower limb muscles, the algorithms detected several performance indicators demonstrating differential adaptation (shifts in the center of activity, prolonged activation) of specific muscle activation modules and spinal motor pools and increased coactivation of lumbar and sacral segments. The software is integrated at EUROBENCH facilities to benchmark the performance of walking in the exoskeleton from the point of view of changes in the spinal locomotor output.

The electrophysiological properties of hindlimb motoneurons do not differ between male and female rats.

Several studies have reported differences in the morphological characteristics of motoneurons and the contractile properties of motor units of male and female rats. However, differences in spinal motoneuron activity between the sexes are not well understood. This study investigates the electrophysiological properties of spinal α‐motoneurons in male and female Wistar rats under pentobarbital anaesthesia. Fast and slow types of tibial motoneurons were recorded intracellularly in 15 male and 15 female rats, and the measured parameters were compared statistically using two‐way ANOVA and Tukey post hoc tests. The membrane properties, action potential parameters and firing characteristics were not different between sexes, though significant differences were observed in the properties of fast and slow motoneuron types within both sex groups. We conclude that the sex‐related differences observed in motor performance between male and female rats are largely due to differences in muscle mass, the proportion of muscle fibre types and the related motor unit contractile properties, while the mechanisms of motor control dependent on the electrophysiological activity of motoneurons are similar between the sexes. These findings are significant, as they indicate that results of experiments investigating electrophysiological properties can be reliably compared between sexes.

Finger Movement Recognition via High-Density Electromyography of Intrinsic and Extrinsic Hand Muscles

Surface electromyography (sEMG) is commonly used to observe the motor neuronal activity within muscle fibers. However, decoding dexterous body movements from sEMG signals is still quite challenging. In this paper, we present a high-density sEMG (HD-sEMG) signal database that comprises simultaneously recorded sEMG signals of intrinsic and extrinsic hand muscles. Specifically, twenty able-bodied participants performed 12 finger movements under two paces and three arm postures. HD-sEMG signals were recorded with a 64-channel high-density grid placed on the back of hand and an 8-channel armband around the forearm. Also, a data-glove was used to record the finger joint angles. Synchronisation and reproducibility of the data collection from the HD-sEMG and glove sensors were ensured. The collected data samples were further employed for automated recognition of dexterous finger movements. The introduced dataset offers a new perspective to study the synergy between the intrinsic and extrinsic hand muscles during dynamic finger movements. As this dataset was collected from multiple participants, it also provides a resource for exploring generalized models for finger movement decoding.

VEGF is an essential retrograde trophic factor for motoneurons

VEGF was initially discovered due to its angiogenic activity and therefore named "vascular endothelial growth factor." However, its more recently discovered neurotrophic activity may be evolutionarily more ancient. Our previous work showed that all the changes produced by axotomy on the firing activity and synaptic inputs of abducens motoneurons were completely restored after VEGF administration. Therefore, we hypothesized that the lack of VEGF delivered by retrograde transport from the periphery should also affect the physiology of otherwise intact abducens motoneurons. For VEGF retrograde blockade, we chronically applied a neutralizing VEGF antibody to the lateral rectus muscle. Recordings of extracellular single-unit activity and eye movements were made in alert cats before and after the application of the neutralizing antibody. Our data revealed that intact, noninjured abducens motoneurons retrogradely deprived of VEGF exhibited noticeable changes in their firing pattern. There is a general decrease in firing rate and a significant reduction in eye position and eye velocity sensitivity (i.e., a decrease in the tonic and phasic components of their discharge, respectively). Moreover, by means of confocal immunocytochemistry, motoneurons under VEGF blockade showed a marked reduction in the density of afferent synaptic terminals contacting with their cell bodies. Altogether, the present findings demonstrate that the lack of retrogradely delivered VEGF renders abducens motoneurons into an axotomy-like state. This indicates that VEGF is an essential retrograde factor for motoneuronal synaptic drive and discharge activity.