Innervation Of Muscle Research Articles

Age and initial position affect movement biomechanics in sit to walk Transitions: Lower limb muscle Activity and joint moments

Facilitating forward movement while maintaining dynamic stability during transitions like sit-to-walk (STW) requires coordination from many muscles. Age-related muscle, sensory, and neural decline can introduce compensatory biomechanics when completing STW, such as adjusting initial foot position or rising with arm support. Many previous STW studies restrict arm movement and prescribe symmetric foot positions, therefore the purpose of this study was to quantify lower limb muscle excitations and joint moments in STW transitions from four initial foot positions [symmetric, posterior offset, wide, narrow] and two arm placements [hands on knees, arms folded] in 15 younger and 15 older adults. Peak knee and ankle joint extension moments, as well as peak electromyography of five bilateral lower-limb muscles were analyzed. In all conditions, older adults had larger knee extension moments, whereas younger adults had larger ankle plantarflexion moments. Older adults generated larger peak excitation from the knee extensor muscles during rising compared to younger adults, consistent with the higher knee extension moments. Older adults had greater peak dorsiflexor and plantarflexor muscle excitation while rising compared to younger adults. Posterior offset and wide foot positions required the largest peak ankle plantarflexion and knee extension moments and plantarflexor muscle excitation. Arm-supported rising decreased peak knee extensor muscle excitation. In addition, there were interaction effects between age and initial foot position/arm placement for multiple quantities, indicating that the effects of foot and arm placement vary with age. These results inform assessments of movement performance and guidelines for rising given individual lower limb capability.

Physical exercise halts further functional decline in an animal model for Charcot-Marie-Tooth disease 1X at an advanced disease stage.

Charcot-Marie-Tooth (CMT) type 1 neuropathies are the most common inherited diseases of the peripheral nervous system. Although more than 100 causative genes have been identified so far, therapeutic options are still missing. We could previously identify that early-onset physical exercise (voluntary wheel running, VWR) dampens peripheral nerve inflammation, improves neuropathological alterations, and clinical outcome in Cx32def mice, a model for CMT1X. We here investigate the clinical and histopathological effect of late-onset exercise in Cx32def mice at an advanced disease stage. Nine-month-old Cx32def mice were allowed to run for 4 days/week on a commercially available running wheel for 3 months, with timely limited access to running wheels, representing a running distance of ~2000 m. Control mutants had no access to running wheels. Afterward, mice were investigated by distinct functional tests and by immunohistochemical and electron microscopical techniques. We found that late-onset physical exercise (late VWRlim) prevented the robust functional decline in 12-month-old Cx32def mice. This was accompanied by improved neuromuscular innervation of distal muscles and axonal preservation in femoral quadriceps nerves. In contrast to a "pre-symptomatic" start of physical exercise in Cx32def mice, late-onset VWR did not alter nerve inflammation and myelin thickness at 12 months of age. We conclude that VWR has robust beneficial effects on nerve function in Cx32def mice, even when applied at a progressed disease stage. These results have important translational implications, suggesting that physical exercise might be an effective treatment option for CMT1 patients, even when disease symptoms have already progressed.

Innovative spiral nerve conduits: Addressing nutrient transport and cellular activity for critical-sized nerve defects

Large-gap nerve defects require nerve guide conduits (NGCs) for complete regeneration and muscle innervation. Many NGCs have been developed using various scaffold designs and tissue engineering strategies to promote axon regeneration. Still, most are tubular with inadequate pore sizes and lack surface cues for nutrient transport, cell attachment, and tissue infiltration. This study developed a porous spiral NGC to address these issues using a 3D-printed thermoplastic polyurethane (TPU) fiber lattice. The lattice was functionalized with poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) electrospun aligned (aPHBV) and randomly (rPHBV) oriented nanofibers to enhance cellular activity. TPU lattices were made with 25 %, 35 %, and 50 % infill densities to create scaffolds with varied mechanical compliance. The fabricated TPU/PHBV spiral conduits had significantly higher surface areas (25 % TPU/PHBV: 698.97 mm2, 35 % TPU/PHBV: 500.06 mm2, 50 % TPU/PHBV: 327.61 mm2) compared to commercially available nerve conduits like Neurolac™ (205.26 mm2). Aligned PHBV nanofibers showed excellent Schwann cell (RSC96) adhesion, proliferation, and neurogenic gene expression for all infill densities. Spiral TPU/PHBV conduits with 25 % and 35 % infill densities exhibited Young's modulus values comparable to Neurotube® and ultimate tensile strength like acellular cadaveric human nerves. A 10 mm sciatic nerve defect in Wistar rats treated with TPU/aPHBV NGCs demonstrated muscle innervation and axon healing comparable to autografts over 4 months, as evaluated by gait analysis, functional recovery, and histology. The TPU/PHBV NGC developed in this study shows promise as a treatment for large-gap nerve defects.

Frequency-dependent effects of superimposed NMES on spinal excitability in upper and lower limb muscles

Superimposing neuromuscular electrical stimulation (NMES) on voluntary contractions has proven to be highly effective for improving muscle strength and performance. These improvements might involve specific adaptations occurring at cortical and spinal level. The effects of NMES on corticospinal activation seem to be frequency dependent and differ between upper and lower limb muscles. The aim of this study was to investigate acute responses in spinal excitability, as measured by H-reflex amplitude of flexor carpi radialis (FCR) and soleus (SOL) muscles, after NMES superimposed on voluntary contractions (NMES + ISO) at two different pulse frequencies (40 and 80 Hz). Conditions involved fifteen intermittent contractions at submaximal level. Before and after each condition, H-reflexes were elicited in FCR and SOL muscles.H-reflex amplitudes increased in FCR and SOL following both NMES + ISO at 40 and 80 Hz. The potentiation of the H-reflex was greater following the 40 Hz condition compared to 80 Hz, although no differences between muscles emerged.These findings indicated that superimposing NMES has an excitatory effect on spinal motoneurons in both upper and lower limb muscles with an overall greater response after low frequency NMES. Such facilitation could be associated to enhanced somatosensory stimuli conjunctly with higher supraspinal downward commands.

Bioactive MXene hydrogel promotes structural and functional regeneration of skeletal muscle through improving autophagy and muscle innervation

Complete skeletal muscle regeneration after traumatic injuries remains a challenge due to impaired regenerative capability and dysregulated microenvironments. Autophagy plays a crucial role in the muscle regeneration process by regulating myogenic and non-myogenic cells. Herein, we report a bioactive MXene hydrogel (FPGM) capable of upregulating autophagy and increasing muscle innervation to restore skeletal muscle structure and function. FPGM possessed excellent electrical conductivity, tissue adhesive ability and antioxidation, which could eliminate excess reactive oxygen species to reduce oxidative stress and decrease the secretion of pro-inflammatory cytokine. FPGM upregulated the autophagy level of myoblasts and promoted the migration and tube formation of endothelial cells as well as myogenic differentiation with negligible toxicity. FPGM accelerated muscle fiber formation and skeletal muscle regeneration by improving autophagy, which could regulate microenvironment through raising M2 macrophages to alleviate excessive inflammation, facilitating angiogenesis and decreasing fibrous scar tissue formation in vivo. Importantly, FPGM could efficiently restore muscle function by improving muscle innervation, tibialis anterior compound muscle action potential amplitude and neuromuscular conduction. This work demonstrates that bioactive MXene hydrogel should be a promising candidate for complete skeletal muscle regeneration.

Aging Skeletal Muscles: What Are the Mechanisms of Age-Related Loss of Strength and Muscle Mass, and Can We Impede Its Development and Progression?

As we age, we lose muscle strength and power, a condition commonly referred to as sarcopenia (ICD-10-CM code (M62.84)). The prevalence of sarcopenia is about 5–10% of the elderly population, resulting in varying degrees of disability. In this review we emphasise that sarcopenia does not occur suddenly. It is an aging-induced deterioration that occurs over time and is only recognised as a disease when it manifests clinically in the 6th–7th decade of life. Evidence from animal studies, elite athletes and longitudinal population studies all confirms that the underlying process has been ongoing for decades once sarcopenia has manifested. We present hypotheses about the mechanism(s) underlying this process and their supporting evidence. We briefly review various proposals to impede sarcopenia, including cell therapy, reducing senescent cells and their secretome, utilising targets revealed by the skeletal muscle secretome, and muscle innervation. We conclude that although there are potential candidates and ongoing preclinical and clinical trials with drug treatments, the only evidence-based intervention today for humans is exercise. We present different exercise programmes and discuss to what extent the interindividual susceptibility to developing sarcopenia is due to our genetic predisposition or lifestyle factors.

Anatomy of the Achilles tendon-Apictorial review.

The Achilles tendon (AT) is the strongest tendon of the human body. The knowledge of AT anatomy is abasic prerequisite for the successful treatment of acute and chronic lesions. The structure of the AT results from acomplicated fusion of three parts: the tendons of the medial and lateral gastrocnemius and the soleus muscles. From proximal to distal, the tendon fibers twist in along spiral into aroughly 90° internal rotation. The tendon is narrowest approximately 5-7 cm above its calcaneal insertion and from there it expands again. The topography of the footprints of the individual AT components reflects the tendon origins. The anterior (deep) AT fibers insert into the middle third of the posterior aspect of the calcaneal tuberosity, the posterior (superficial) fibers pass over the calcaneal tuberosity and fuse with the plantar aponeurosis. Adeep calcaneal bursa is interposed between the calcaneal tuberosity and the AT anterior surface. The AT has no synovial sheath but is covered along its entire length with asliding connective tissue, the paratenon which is, however, absent on its anterior surface. The AT is supplied by the posterior tibial artery (PTA) and the peroneal artery (PA). Motor innervation of the triceps surae muscle is provided by fibers of the tibial nerve which also gives off sensitive fibers for the AT. Sensitive innervation is also provided via the sural nerve. The sural nerve crosses the AT approximately 11 cm proximal to the calcaneal tuberosity. The forces acting on the AT during exercise may be up to 12 times the body weight. Physiological stretching of AT collagen fibers ranges between 2% and 4% of its length. Stretching of the tendon over 4% results in microscopic failure and stretching beyond 8% in macroscopic failure.

A meta-analysis on the improvement of vocal function in unilateral vocal cord paralysis by reinnervation of the recurrent laryngeal nerve

Objective:To conduct a systematic description and meta-analysis of the treatment of unilateral vocal cord paralysis（UVCP） with recurrent laryngeal nerve reinnervation through literature search, and to analyze the therapeutic effect of recurrent laryngeal nerve reinnervation on improving vocal function in UVCP. Methods:Electronic databases Pubmed, Web of Science, EMBASE, Cochrane Library, CNKI, and Wanfang databases were searched using relevant keywords and screened in strict accordance with the inclusion and exclusion criteria, and quality evaluations were conducted. Reported treatment outcomes were measured by relevant data extracted from literature, such as auditory perception assessment（GRBAS）, voice handicap index（VHI）, maximal phonation time（MPT）, jitter, shimmer, and noise harmonic ratio（NHR）, etc. Meta-analysis was performed by Revman5.3 and heterogeneity was analyzed using fixed effects or random effects models. Results:Eight articles were included in this study, all of which showed that the postoperative maximum phonation time of patients was significantly prolonged compared to preoperative, while the postoperative GRBAS score, Jitter, Shimmer, and NHR decreased compared to preoperative with statistical significance. Conclusion:The innervation of the internal laryngeal muscle was obtained through the reinnervation of the recurrent laryngeal nerve, which effectively improved the patient's vocal function and had a good long-term therapeutic effect. Although there was no difference in the efficacy of surgical methods for reconstructing the recurrent laryngeal nerve, the anastomosis between ansa cervicalis nerve and the recurrent laryngeal nerve is more ideal. Further randomized controlled studies with longer follow-up periods and larger samples will increase the credibility of their effectiveness.

Fish That Fish for Fish-A Peculiar Location of "Fishing Motoneurons" in the Striated Frogfish Antennarius striatus.

In lophiform teleosts, the first dorsal fin has evolved as a specialized structure called the "illicium" equipped with the esca, which is a modified skin flap used to attract small fish for predation. The motor control system of the illicium, however, remained unknown. The present study investigated the innervation of muscles for the illicium and morphology of motoneurons innervating them in the striated frogfish Antennarius striatus. We found that the dorsal ramus of occipital nerve innervates the muscles. Motoneurons for the illicium are present in the dorsolateral zone of ventral horn at the medullo-spinal boundary level, forming a cluster somewhat distinct from other motoneurons of the ventral horn. Motoneurons for the second to fourth dorsal fins and pectoral fin were located in the ventrolateral and ventromedial zones of ventral horn, respectively, whereas those of the dorsal trunk muscle in the dorsomedial zone of ventral horn. Motoneurons for the first dorsal spine of white-spotted pygmy filefish were also investigated for species comparison and were found to locate in the ventrolateral zone of ventral horn, similarly to the motoneurons for the second to fourth dorsal fins of the frogfish. These results suggest that motoneurons for the illicium have become segregated from other motoneurons to be situated in an unusual dorsal position for a motoneuron pool of a dorsal fin, in concert with the evolution of specialized "fishing behavior" performed by the illicium.

243P The effect of Nav1.4 Ile582Val gain-of-function mutation on mouse skeletal muscle excitability is sex specific

243P The effect of Nav1.4 Ile582Val gain-of-function mutation on mouse skeletal muscle excitability is sex specific

Innervation of the muscles of the pelvic limb of the nutria (Myocastor coypus) by nerves originating from the lumbosacral plexus

Abstract Knowledge about the innervation of the pelvic limb is crucial in veterinary sciences, particularly in anesthesiology, diagnostics, and veterinary surgery, where precise knowledge of the nervous system enables effective treatment and interventions. With the growing interest of veterinarians in studies of the rodent, expanding knowledge of the neuroanatomy of these animals is key to improving veterinary care and treatment efficacy. The aim of our study was to analyze the innervation of the pelvic limb muscles in the nutria (Myocastor coypus). Our research demonstrated that these muscles are innervated by motor fibers from nerves such as the femoral nerve, the obturator nerve, the sciatic nerve, and the cranial and caudal gluteal nerves. We also determined the origin of these nerves, indicating that they stem from the ventral roots of the spinal nerves from L3 to S1, knowing that the nutria has six lumbar vertebrae. Conclusions from such analyses can contribute to a deeper understanding of the evolutionary anatomy of the nervous system in various mammal groups and the development of more precise diagnostic and therapeutic methods in veterinary medicine.

Assessing the Feasibility of EMG Biofeedback to Reduce the Upper Trapezius Muscle Excitation during a Seated Row Exercise, a Non-randomized Comparative Study.

The upper trapezius muscle is often excessively excited during resistance training exercises, increasing the shoulder's liability to musculoskeletal disorders of individuals participating in overhead sports or throwing activities. Different approaches have been proposed for reducing the potentially harmful loading of the upper trapezius. None, however, has been devised to deal directly with the main culprit: the muscle excitation. This non-randomized comparative study explores the feasibility of biofeedback based on surface electromyograms (EMGs) in suppressing undue excitation of the upper trapezius during a seated row exercise. Eight male volunteers were instructed to perform the wide-grip seated row exercise without and with the EMG biofeedback of the upper trapezius. Surface EMGs from the three portions of the trapezius and the serratus anterior were sampled with pairs of surface electrodes. A triaxial accelerometer was positioned on the weight stack for the identification of the exercise phase and repetition. This study showed that during the "with biofeedback" condition, the participants were able to activate the upper trapezius and serratus anterior to a lower degree (~ 10%) compared to the "without biofeedback" condition. Future studies should explore if this can lead to greater gains in muscle performance and/or reduce the risk of shoulder injury.

BK channels promote action potential repolarization in skeletal muscle but contribute little to myotonia

Patients with myotonia congenita suffer from slowed relaxation of muscle (myotonia), due to hyperexcitability caused by loss-of-function mutations in the ClC-1 chloride channel. A recent study suggested that block of large-conductance voltage- and Ca2+- activated K+ channels (BK) may be effective as therapy. The mechanism underlying efficacy was suggested to be lessening of the depolarizing effect of build-up of K+ in t-tubules of muscle during repetitive firing. BK channels are widely expressed in the nervous system and have been shown to play a central role in regulation of excitability, but their contribution to muscle excitability has not been determined. We performed intracellular recordings as well as force measurements in both wild type and BK−/− mouse extensor digitorum longus muscles. Action potential width was increased in BK−/− muscle due to slowing of repolarization, consistent with the possibility K+ build-up in t-tubules is lessened by block of BK channels in myotonic muscle. However, there was no difference in the severity of myotonia triggered by block of muscle Cl− channels with 9-anthracenecarboxylic acid (9AC) in wild type and BK−/− muscle fibers. Further study revealed no difference in the interspike membrane potential during repetitive firing suggesting there was no reduction in K+ build-up in t-tubules of BK−/− muscle. Force recordings following block of muscle Cl− channels demonstrated little reduction in myotonia in BK−/− muscle. In contrast, the current standard of care, mexiletine, significantly reduced myotonia. Our data suggest BK channels regulate muscle excitability, but are not an attractive target for therapy of myotonia.

A Moderate Blood Flow Restriction Pressure Does Not Affect Maximal Strength or Neuromuscular Responses.

Lubiak, SM, Lawson, JE, Gonzalez Rojas, DH, Proppe, CE, Rivera, PM, Hammer, SM, Trevino, MA, Dinyer-McNeely, TK, Montgomery, TR, Olmos, AA, Sears, KN, Bergstrom, HC, Succi, PJ, Keller, JL, and Hill, EC. A moderate blood flow restriction pressure does not affect maximal strength or neuromuscular responses. J Strength Cond Res XX(X): 000-000, 2024-The purpose of this study was to examine the acute effects of blood flow restriction (BFR) applied at 60% of total arterial occlusion pressure (AOP) on maximal strength. Eleven college-aged female subjects completed two testing sessions of maximal unilateral concentric, isometric, and eccentric leg extension muscle actions performed with and without BFR. Separate 3 (mode [isometric, concentric, eccentric]) × 2 (condition [BFR, no BFR]) × 2 (visit [2, 3]) repeated-measures analysis of variances were used to examine mean differences in maximal strength, neuromuscular function, rating of perceived exertion (RPE), and pain. For maximal strength (collapsed across condition and visit), isometric (128.5 ± 22.7 Nm) and eccentric (114.5 ± 35.4 Nm) strength were greater than concentric maximal strength (89.3 ± 22.3 Nm) (p < 0.001-0.041). Muscle excitation relative (%) to isometric non-BFR was greater during the concentric (108.6 ± 31.5%) than during the eccentric (86.7 ± 29.2%) (p = 0.045) assessments but not different than isometric (93.4 ± 17.9%) (p = 0.109) assessments, collapsed across condition and visit. For RPE, there was an interaction such that RPE was greater during non-BFR (4.3 ± 1.7) than during BFR (3.7 ± 1.7) (p = 0.031) during the maximal concentric strength assessments. Furthermore, during maximal strength assessments performed with BFR, isometric RPE (5.8 ± 1.9) was greater than concentric (3.7 ± 1.7) (p = 0.005) and eccentric (4.6 ± 1.9) (p = 0.009) RPE. Finally, pain was greater during the isometric (2.8 ± 2.1 au) than during the concentric (1.8 ± 1.5 au) (p = 0.016), but not eccentric, maximal strength assessments (2.1 ± 1.6 au) (p = 0.126), collapsed across condition and visit. The application of BFR at 60% AOP did not affect concentric, isometric, or eccentric maximal strength or neuromuscular function. Trainers, clinicians, and researchers can prescribe exercise interventions relative to a restricted (when using a moderate AOP) or nonrestricted assessment of maximal strength.

Electroneuromyographic examination of pelvic floor muscle dysfunction in patients with descending perineum syndrome

Aim: to assess the functional state of the pelvic floor muscles and their innervation in patients with descending perineum syndrome, manifested simultaneously by obstructive defecation and chronic neurogenic pelvic pain.Materials and methods: in 2022–2023, 51 patients (40 (78.4 %) women, 11 (21.6 %) men; age 50.9 ± 14.5 years) with pelvic organ prolapse, manifested by obstructive defecation and chronic neurogenic pelvic pain were examined at the Ryzhikh National Medical Research Centre for Coloproctology. All patients underwent high-resolution anorectal manometry and stimulation electroneuromyography according to a comprehensive neurophysiological protocol using a St. Mark’s electrode.Results: manometric patterns of functional defecation disorders were detected in 40 (78.4 %) patients, in the rest they were confirmed by defecography data and a negative evacuation test according to the Rome criteria IV. With stimulation electroneuromyography, neuropathy was detected in 68.6 % of cases by increasing the latency of the M-response of the pudendal nerve on the right or left. Complex neurophysiological diagnostics made it possible to additionally identify neuropathy in another 25.5 % of patients: according to changes in the mixed reciprocating reflex response (mixed feedback-reflex response) (efferent pathway) — in 17.7 % of cases; according to changes in the bulbocavernous reflex (efferent and afferent pathways) — in 7.8 % of cases. That is, neuropathy was determined in 94.1 % of patients in total.Conclusions:Functional diagnostic methods are an effective tool for studying the state of the pelvic floor muscle structures and their innervation and make it possible to identify pathogenetic links of disorders, the clinical manifestations of which are anal incontinence, neurogenic pelvic pain and proctogenic constipation in the form of obstructive defecation.Stimulation electroneuromyography makes it possible to detect disturbed innervation of the pelvic floor muscles and anal sphincter in the standard study of the M-response in 68.6 % of cases with perineal prolapse syndrome with a combination of proctogenic disorders and neurogenic pelvic pain. The use of a comprehensive neurophysiological protocol makes it possible to detect innervation disorders in 94.1 % of cases.

Reduced Clavicle Length Indicates the Severity of Scapular Misalignment in Obstetric Brachial Plexus Lesions.

(1) Background: Although most brachial plexus birth palsies show some spontaneous recovery, secondary operations are likely to follow. Accordingly, due to the loss of muscle innervation, the growth of the affected limb and the shoulder girdle is reduced. This is associated with pathological scapula positioning and rotation. The objective of this work was to clarify the relationship between length differences of the two clavicles and different types of scapular dyskinesia. (2) Methods: Twenty-five patients suffering from brachial plexus birth palsy were included in this retrospective study. There were eighteen female and seven male patients with a mean age of 10 years (2 to 23 years). CT scans of the thoracic cage, including both shoulder joints and both clavicles, were obtained preoperatively between 2010 and 2012. Radiographic measurements were taken of the axial plane and 3D reconstructions were produced. Functional evaluations of possible movement and scapular dyskinesia were performed. (3) Results: We found an increasing difference in the length of the clavicle (both in absolute and relative terms) in the children with more pronounced scapular dyskinesia. Additionally, with increasing clavicle length differences, the scapula was positioned in a deteriorated angle compared to the healthy side. Significant positive correlations were identified for the age and absolute difference of the clavicle length and the length and width of the scapula on the affected side. (4) Conclusion: Scapular dyskinesia, which is a common finding in brachial plexus birth palsy, is strongly related to reduced clavicle growth. Reduced clavicle length (which is a relatively easily examinable parameter) compared to the healthy side can be used to estimate the extent of scapular malpositioning on the thoracic cage. The extent and severity of scapular dyskinesia increases with augmented differences in the length of the clavicle.

The Combined Delivery of the Vegf, Ang, and Gdnf Genes Stimulates Angiogenesis and Improves Post-Ischemic Innervation and Regeneration in Skeletal Muscle.

In this study, the effects of different combinations of the genes Vegf, Ang, and Gdnf injected both using direct virus-mediated injection (adenovirus, Ad5) and umbilical cord blood mononuclear cells (UCBCs) on the processes of stimulation of post-ischemic innervation, angiogenesis, and regeneration in skeletal muscle were investigated in a rat hindlimb chronic ischemia model. It was shown that more pronounced stimulation of angiogenesis and restoration of post-ischemic innervation were achieved both in the early (28 days post-ischemia, dpi) and late (42 dpi) terms of the experiment in the calf muscle when UCBCs delivered the combination of Ad5-Vegf and Ad5-Ang compared to the direct injection of the same vector combination into the area of ischemia. At the same time, the inclusion of Ad5-Gdnf in the combination of Ad5-Vegf and Ad5-Ang directly injected or administered by UCBCs provided a significant increase in the number of centronuclear muscle fibers, indicating stimulation of post-ischemic reparative myogenesis. This study allowed us to determine the most effective gene combinations for angiogenesis and neurogenesis, which, in the future, may serve as the basis for the development of gene and gene cell products for the treatment of chronic lower limb ischemia.

Enhancer AAVs for targeting spinal motor neurons and descending motor pathways in rodents and macaque.

Experimental access to cell types within the mammalian spinal cord is severely limited by the availability of genetic tools. To enable access to lower motor neurons (LMNs) and LMN subtypes, which function to integrate information from the brain and control movement through direct innervation of effector muscles, we generated single cell multiome datasets from mouse and macaque spinal cords and discovered putative enhancers for each neuronal population. We cloned these enhancers into adeno-associated viral vectors (AAVs) driving a reporter fluorophore and functionally screened them in mouse. The most promising candidate enhancers were then extensively characterized using imaging and molecular techniques and further tested in rat and macaque to show conservation of LMN labeling. Additionally, we combined enhancer elements into a single vector to achieve simultaneous labeling of upper motor neurons (UMNs) and LMNs. This unprecedented LMN toolkit will enable future investigations of cell type function across species and potential therapeutic interventions for human neurodegenerative diseases.

Improvement of Motor Task Performance: Effects of Verbal Encouragement and Music-Key Results from a Randomized Crossover Study with Electromyographic Data.

External motivational stimuli have been shown to improve athletic performance. However, the neurophysiological mechanisms underlying this improvement remain poorly understood. This randomized crossover study investigated the effects of music and verbal encouragement on measures of muscle excitation and myoelectric manifestations of fatigue in the biceps brachii and brachioradialis muscles during an endurance task. Fifteen untrained (mean age 29.57 ± 2.77 years) and 13 trained individuals (mean age 32.92 ± 2.90 years) were included. The endurance task, performed to exhaustion, consisted of keeping the dominant arm flexed to 90 degrees while holding a dumbbell loaded to 80% of 1RM with a supine grip in three randomized conditions: standard, with self-selected music, and with verbal encouragement. The untrained subjects showed an increase in task duration of 15.26% (p < 0.003) with music and 15.85% (p < 0.002) with verbal encouragement compared to the condition without external stimuli. There were no significant differences in the myoelectric manifestations of fatigue between the different conditions. Regarding the muscle excitation metrics, although the mean amplitude, peak value, and area under the curve remained unchanged across conditions, a significant reduction in the trend coefficient, indicating motor unit recruitment over time, was observed with both music (biceps brachii: -10.39%, p < 0.001; brachioradialis: -9.40%, p < 0.001) and verbal encouragement (biceps brachii: -7.61%, p < 0.001; brachioradialis: -6.51%, p < 0.001) compared to the standard condition. For the trained participants, no significant differences were observed between conditions in terms of task duration and outcome measures related to muscle excitation and myoelectric manifestations of fatigue, suggesting the possible presence of a ceiling effect on motivation. These results highlight the important role of external motivational stimuli, such as music and verbal encouragement, in improving task performance in untrained subjects, probably through more effective and efficient recruitment of motor units.

Characterization of ClC-1 chloride channels in zebrafish: a new model to study myotonia.

The function of the chloride channel ClC-1 is crucial for the control of muscle excitability. Thus, reduction of ClC-1 functions by CLCN1 mutations leads to myotonia congenita. Many different animal models have contributed to understanding the myotonia pathophysiology. However, these models do not allow in vivo screening of potentially therapeutic drugs, as the zebrafish model does. In this work, we identified and characterized the two zebrafish orthologues (clc-1a and clc-1b) of the ClC-1 channel. Both channels are mostly expressed in the skeletal muscle as revealed by RT-PCR, western blot, and electrophysiological recordings of myotubes, and clc-1a is predominantly expressed in adult stages. Characterization in Xenopus oocytes shows that the zebrafish channels display similar anion selectivity and voltage dependence to their human counterparts. However, they show reduced sensitivity to the inhibitor 9-anthracenecarboxylic acid (9-AC), and acidic pH inverts the voltage dependence of activation. Reduction of clc-1a/b expression hampers spontaneous and mechanically stimulated movement, which could be reverted by expression of human ClC-1 but not by some ClC-1 containing myotonia mutations. Treatment of clc-1-depleted zebrafish with mexiletine, a typical drug used in human myotonia, improves the motor behaviour. Our work extends the repertoire of ClC channels to evolutionary structure-function studies and proposes the zebrafish clcn1 crispant model as a simple tool to find novel therapies for myotonia. KEY POINTS: We have identified two orthologues of ClC-1 in zebrafish (clc-1a and clc-1b) which are mostly expressed in skeletal muscle at different developmental stages. Functional characterization of the activity of these channels reveals many similitudes with their mammalian counterparts, although they are less sensitive to 9-AC and acidic pH inverts their voltage dependence of gating. Reduction of clc-1a/b expression hampers spontaneous and mechanically stimulated movement which could be reverted by expression of human ClC-1. Myotonia-like symptoms caused by clc-1a/b depletion can be reverted by mexiletine, suggesting that this model could be used to find novel therapies for myotonia.