RESUMEN
OBJECTIVE: There is little proof to determine the features of the muscles' motor unit potentials (MUPs) in children with poor posture. Current evaluation could be of value for future studies as a reference. The purpose was to detect the impact of rounded back posture on the characteristics of the MUPs and fascicle length of the shoulder retractors in children. METHODS: Participants in this study were 60 children (boys and girls), their ages were from 7 to 10 years old. Children were allocated into healthy children group (A) and rounded back posture group (B). MUPs and fascicle length of middle trapezius were assessed by electromyography and ultrasonography respectively. RESULTS: When compared to the normal group, the rounded back group's right and left middle trapezius MUPs count and amplitude significantly increased. As regards to the middle trapezius MUPs duration between the two groups, there was no significant difference. Also, the rounded back posture group exhibited significantly lower fascicle length in middle trapezius of both sides than the normal group. CONCLUSION: Forward shoulder posture is accompanied by atypical middle trapezius MUPs characteristics and also lowered fascicle length. Thus, children with forward-leaning posture could increase the likelihood of developing any of the many shoulder disorders.
Asunto(s)
Electromiografía , Postura , Hombro , Humanos , Niño , Femenino , Masculino , Postura/fisiología , Hombro/fisiología , Hombro/diagnóstico por imagen , Electromiografía/métodos , Músculos Superficiales de la Espalda/fisiología , Músculos Superficiales de la Espalda/diagnóstico por imagen , Ultrasonografía/métodos , Neuronas Motoras/fisiologíaRESUMEN
Finding optimal bipartite matchings-e.g., matching medical students to hospitals for residency, items to buyers in an auction, or papers to reviewers for peer review-is a fundamental combinatorial optimization problem. We found a distributed algorithm for computing matchings by studying the development of the neuromuscular circuit. The neuromuscular circuit can be viewed as a bipartite graph formed between motor neurons and muscle fibers. In newborn animals, neurons and fibers are densely connected, but after development, each fiber is typically matched (i.e., connected) to exactly one neuron. We cast this synaptic pruning process as a distributed matching (or assignment) algorithm, where motor neurons "compete" with each other to "win" muscle fibers. We show that this algorithm is simple to implement, theoretically sound, and effective in practice when evaluated on real-world bipartite matching problems. Thus, insights from the development of neural circuits can inform the design of algorithms for fundamental computational problems.
Asunto(s)
Algoritmos , Neuronas Motoras , Neuronas Motoras/fisiología , Animales , Humanos , Redes Neurales de la Computación , Modelos NeurológicosRESUMEN
INTRODUCTION: Reliable, noninvasive early diagnostics of neuromuscular function in Bell's palsy, which causes facial paralysis and reduced quality of life, remain to be established. Here, we aimed to evaluate the utility of the motor unit number index (MUNIX) for the quantitative electrophysiological assessment of early-stage Bell's palsy, its correlation with clinical assessments, changes following treatment, and association with clinical prognosis. METHODS: MUNIX measures were recorded from the bilateral zygomaticus, orbicularis oculi, and orbicularis oris muscles of 10 healthy individuals and 64 patients with Bell's palsy. The patients were assessed by two specialist neurologists using the House-Brackmann and Sunnybrook Facial Grading Systems. Repeat assessments were performed on 20 patients with Bell's palsy who received treatment. Additionally, the 64 patients were reassessed using clinical scales after a 1-month interval. RESULTS: The MUNIX values of the main affected muscles on the affected side were lower than those on the healthy side in patients with Bell's palsy (p < .05). The MUNIX measurements significantly correlated with the clinical facial nerve palsy scale scores (p < .05). Significant improvements were observed in the MUNIX values on repeat testing following treatment (p < .05). The baseline motor unit size index (the compound muscle action potential amplitude divided by MUNIX) was positively associated with improved clinical presentation after 1 month (p < .05). CONCLUSION: MUNIX can be used as an electrophysiological biomarker for the quantitative assessment of facial nerve palsy and treatment response, and as a prognostic biomarker, in patients with early Bell's palsy, and is recommended as a complement to conventional neurophysiological examinations.
Asunto(s)
Parálisis de Bell , Electromiografía , Humanos , Parálisis de Bell/fisiopatología , Parálisis de Bell/diagnóstico , Masculino , Femenino , Adulto , Persona de Mediana Edad , Electromiografía/métodos , Músculos Faciales/fisiopatología , Adulto Joven , Anciano , Biomarcadores , Neuronas Motoras/fisiología , Diagnóstico Precoz , Potenciales de Acción/fisiologíaRESUMEN
Patellar tendinopathy (PT) typically affects jumping-sport athletes with functional impairments frequently observed. Alterations to the functional organization of corticomotor neurons within the motor cortex that project to working muscles are evident in some musculoskeletal conditions and linked to functional impairments. We aimed to determine if functional organization of corticomotor neuron projections differs between athletes with PT and asymptomatic controls, and if organization is associated with neuromuscular control. We used a cross-sectional design, and the setting was Monash Biomedical Imaging. Basketball and volleyball athletes with (n = 8) and without PT (n = 8) completed knee extension and ankle dorsiflexion force matching tasks while undergoing fMRI. We determined functional organization via identification of the location of peak corticomotor neuron activation during respective tasks (expressed in X, Y, and Z coordinates) and calculated force matching accuracy for both tasks to quantify neuromuscular control. We observed significant interactions between group and coordinate plane for functional organization of corticomotor projections to knee extensors (p < 0.001) and ankle dorsiflexors (p = 0.016). Compared to controls, PT group peak corticomotor activation during the knee extension task was 9.6 mm medial (p < 0.001) and 5.2 mm posterior (p = 0.036), and during the ankle dorsiflexion task 8.2 mm inferior (p = 0.024). In the PT group, more posterior Y coordinate peak activation location during the knee extension task was associated with greater task accuracy (r = 0.749, p = 0.034). Functional organization of corticomotor neurons differed in jumping athletes with PT compared to controls. Links between functional organization and neuromuscular control in the PT group suggest organizational differences may be relevant to knee extension neuromuscular control preservation.
Asunto(s)
Baloncesto , Imagen por Resonancia Magnética , Corteza Motora , Tendinopatía , Voleibol , Humanos , Voleibol/fisiología , Baloncesto/fisiología , Corteza Motora/fisiología , Corteza Motora/fisiopatología , Estudios Transversales , Tendinopatía/fisiopatología , Masculino , Adulto Joven , Femenino , Adulto , Neuronas Motoras/fisiología , Ligamento Rotuliano/fisiopatología , Ligamento Rotuliano/fisiología , Atletas , Estudios de Casos y ControlesRESUMEN
EMG filling curve characterizes the EMG filling process and EMG probability density function (PDF) shape change for the entire force range of a muscle. We aim to understand the relation between the physiological and recording variables, and the resulting EMG filling curves. We thereby present an analytical and simulation study to explain how the filling curve patterns relate to specific changes in the motor unit potential (MUP) waveforms and motor unit (MU) firing rates, the two main factors affecting the EMG PDF, but also to recording conditions in terms of noise level. We compare the analytical results with simulated cases verifying a perfect agreement with the analytical model. Finally, we present a set of real EMG filling curves with distinct patterns to explain the information about MUP amplitudes, MU firing rates, and noise level that these patterns provide in the light of the analytical study. Our findings reflect that the filling factor increases when firing rate increases or when newly recruited motor unit have potentials of smaller or equal amplitude than the former ones. On the other hand, the filling factor decreases when newly recruited potentials are larger in amplitude than the previous potentials. Filling curves are shown to be consistent under changes of the MUP waveform, and stretched under MUP amplitude scaling. Our findings also show how additive noise affects the filling curve and can even impede to obtain reliable information from the EMG PDF statistics.
Asunto(s)
Potenciales de Acción , Algoritmos , Simulación por Computador , Electromiografía , Neuronas Motoras , Músculo Esquelético , Relación Señal-Ruido , Electromiografía/métodos , Humanos , Neuronas Motoras/fisiología , Músculo Esquelético/fisiología , Potenciales de Acción/fisiología , Contracción Muscular/fisiología , Reproducibilidad de los Resultados , Reclutamiento Neurofisiológico/fisiología , Modelos EstadísticosRESUMEN
Motoneuronal persistent inward currents (PICs) are facilitated by neuromodulatory inputs but are highly sensitive to local inhibitory circuits. Estimates of PICs are reduced by group Ia reciprocal inhibition, and increased with the diffuse actions of neuromodulators released during remote muscle contraction. However, it remains unknown how motoneurons function in the presence of simultaneous excitatory and inhibitory commands. To probe this topic, we investigated motor unit discharge patterns and estimated PICs during voluntary co-contraction of ankle muscles, which simultaneously demands the contraction of agonist-antagonist pairs. Twenty participants performed triangular ramps of both co-contraction (simultaneous dorsiflexion and plantar flexion) and isometric dorsiflexion to a peak of 30% of their maximum muscle activity from a maximal voluntary contraction. Motor unit spike trains were decomposed from high-density surface EMG activity recorded from tibialis anterior using blind source separation algorithms. Voluntary co-contraction altered motor unit discharge rate characteristics. Discharge rate at recruitment and peak discharge rate were modestly reduced (â¼6% change; P < 0.001; d = 0.22) and increased (â¼2% change; P = 0.001, d = -0.19), respectively, in the entire dataset but no changes were observed when motor units were tracked across conditions. The largest effects during co-contraction were that estimates of PICs (ΔF) were reduced by â¼20% (4.47 vs. 5.57 pulses per second during isometric dorsiflexion; P < 0.001, d = 0.641). These findings suggest that, during voluntary co-contraction, the inhibitory input from the antagonist muscle overcomes the additional excitatory and neuromodulatory drive that may occur due to the co-contraction of the antagonist muscle, which constrains PIC behaviour. KEY POINTS: Voluntary co-contraction is a unique motor behaviour that concurrently provides excitatory and inhibitory synaptic input to motoneurons. Co-contraction of agonist-antagonist pairs alters agonist motor unit discharge characteristics, consistent with reductions in persistent inward current magnitude.
Asunto(s)
Tobillo , Neuronas Motoras , Contracción Muscular , Músculo Esquelético , Humanos , Músculo Esquelético/fisiología , Músculo Esquelético/inervación , Neuronas Motoras/fisiología , Masculino , Adulto , Femenino , Contracción Muscular/fisiología , Tobillo/fisiología , Adulto Joven , Electromiografía , Potenciales de Acción/fisiología , Contracción Isométrica/fisiologíaRESUMEN
Coordinated movement requires the nervous system to continuously compensate for changes in mechanical load across different conditions. For voluntary movements like reaching, the motor cortex is a critical hub that generates commands to move the limbs and counteract loads. How does cortex contribute to load compensation when rhythmic movements are sequenced by a spinal pattern generator? Here, we address this question by manipulating the mass of the forelimb in unrestrained mice during locomotion. While load produces changes in motor output that are robust to inactivation of motor cortex, it also induces a profound shift in cortical dynamics. This shift is minimally affected by cerebellar perturbation and significantly larger than the load response in the spinal motoneuron population. This latent representation may enable motor cortex to generate appropriate commands when a voluntary movement must be integrated with an ongoing, spinally-generated rhythm.
Asunto(s)
Locomoción , Corteza Motora , Neuronas Motoras , Animales , Corteza Motora/fisiología , Ratones , Neuronas Motoras/fisiología , Locomoción/fisiología , Miembro Anterior/fisiología , Masculino , Ratones Endogámicos C57BL , Movimiento/fisiología , Médula Espinal/fisiología , Femenino , Cerebelo/fisiologíaRESUMEN
The primary motor cortex does not uniquely or directly produce alpha motoneurone (α-MN) drive to muscles during voluntary movement. Rather, α-MN drive emerges from the synthesis and competition among excitatory and inhibitory inputs from multiple descending tracts, spinal interneurons, sensory inputs, and proprioceptive afferents. One such fundamental input is velocity-dependent stretch reflexes in lengthening muscles, which should be inhibited to enable voluntary movement. It remains an open question, however, the extent to which unmodulated stretch reflexes disrupt voluntary movement, and whether and how they are inhibited in limbs with numerous multiarticular muscles. We used a computational model of a Rhesus Macaque arm to simulate movements with feedforward α-MN commands only, and with added velocity-dependent stretch reflex feedback. We found that velocity-dependent stretch reflex caused movement-specific, typically large and variable disruptions to arm movements. These disruptions were greatly reduced when modulating velocity-dependent stretch reflex feedback (i) as per the commonly proposed (but yet to be clarified) idealized alpha-gamma (α-γ) coactivation or (ii) an alternative α-MN collateral projection to homonymous γ-MNs. We conclude that such α-MN collaterals are a physiologically tenable propriospinal circuit in the mammalian fusimotor system. These collaterals could still collaborate with α-γ coactivation, and the few skeletofusimotor fibers (ß-MNs) in mammals, to create a flexible fusimotor ecosystem to enable voluntary movement. By locally and automatically regulating the highly nonlinear neuro-musculo-skeletal mechanics of the limb, these collaterals could be a critical low-level enabler of learning, adaptation, and performance via higher-level brainstem, cerebellar, and cortical mechanisms.
Asunto(s)
Macaca mulatta , Neuronas Motoras , Reflejo de Estiramiento , Reflejo de Estiramiento/fisiología , Animales , Neuronas Motoras/fisiología , Movimiento/fisiología , Músculo Esquelético/fisiología , Corteza Motora/fisiología , Simulación por Computador , Modelos Neurológicos , Brazo/fisiologíaRESUMEN
Preclinical studies are crucial for developing amyotrophic lateral sclerosis drugs. Current FDA-approved drugs have been created by monitoring limb muscle function and histological analysis of amyotrophic lateral sclerosis model animals. Drug candidates for this disease have yet to be tested for bulbar-onset type due to the limitations of traditional preclinical tools: excessive animal use and discrete detection of disease progress. Here, our study introduces an all-in-one, wireless, integrated wearable system for facilitating continuous drug efficacy assessment of dysphagia-related muscles in animals during natural eating behaviors. By incorporating a kirigami-based strain-isolation mechanism, this device mounted on the skin of animals mitigates electromyography signal contamination caused by unpredictable animal movements. Our findings indicate this system, measuring the progression of motor neuron denervation, offers high precision in monitoring drug effects on dysphagia-responsible bulbar muscles. This study paves the way for more humane and efficient approaches to developing treatment solutions for degenerative neuromuscular diseases.
Asunto(s)
Esclerosis Amiotrófica Lateral , Modelos Animales de Enfermedad , Electromiografía , Dispositivos Electrónicos Vestibles , Esclerosis Amiotrófica Lateral/fisiopatología , Esclerosis Amiotrófica Lateral/tratamiento farmacológico , Animales , Electromiografía/métodos , Evaluación Preclínica de Medicamentos , Trastornos de Deglución/fisiopatología , Trastornos de Deglución/etiología , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/fisiopatología , Músculo Esquelético/inervación , Humanos , Masculino , Neuronas Motoras/efectos de los fármacos , Neuronas Motoras/fisiología , RatasRESUMEN
The sympathetic nervous system controls bodily functions including vascular tone, cardiac rhythm, and the "fight-or-flight response". Sympathetic chain ganglia develop in parallel with preganglionic motor nerves extending from the neural tube, raising the question of whether axon targeting contributes to sympathetic chain formation. Using nerve-selective genetic ablations and lineage tracing in mouse, we reveal that motor nerve-associated Schwann cell precursors (SCPs) contribute sympathetic neurons and satellite glia after the initial seeding of sympathetic ganglia by neural crest. Motor nerve ablation causes mispositioning of SCP-derived sympathoblasts as well as sympathetic chain hypoplasia and fragmentation. Sympathetic neurons in motor-ablated embryos project precociously and abnormally towards dorsal root ganglia, eventually resulting in fusion of sympathetic and sensory ganglia. Cell interaction analysis identifies semaphorins as potential motor nerve-derived signaling molecules regulating sympathoblast positioning and outgrowth. Overall, central innervation functions both as infrastructure and regulatory niche to ensure the integrity of peripheral ganglia morphogenesis.
Asunto(s)
Ganglios Simpáticos , Neuronas Motoras , Cresta Neural , Células de Schwann , Sistema Nervioso Simpático , Animales , Sistema Nervioso Simpático/embriología , Ratones , Neuronas Motoras/fisiología , Células de Schwann/metabolismo , Cresta Neural/citología , Cresta Neural/metabolismo , Ganglios Simpáticos/citología , Ganglios Espinales , Semaforinas/metabolismo , Semaforinas/genética , Ratones Transgénicos , Neuroglía/metabolismo , FemeninoRESUMEN
Muscles generate varying levels of force by recruiting different numbers of motor units (MUs), and as the force increases, the number of recruited MUs gradually rises. However, current decoding methods encounter difficulties in maintaining a stable and consistent growth trend in MU numbers with increasing force. In some instances, an unexpected reduction in the number of MUs can even be observed as force intensifies. To address this issue, in this study, we propose an enhanced decoding method that adaptively reutilizes MU filters. Specifically, in addition to the normal decoding process, we introduced an additional procedure where MU filters are reused to initialize the algorithm. The MU filters are iterated and adapted to the new signals, aiming to decode motor units that were actually activated but cannot be identified due to heavy superimposition. We tested our method on both simulated and experimental surface electromyogram (sEMG) signals. We simulated isometric signals (10%-70%) with known MU firing patterns using experimentally recorded MU action potentials from forearm muscles and compared the decomposition results to two baseline approaches: convolution kernel compensation (CKC) and fast independent component analysis (fastICA). Our method increased the decoded MU number by a rate of 135.4% ± 62.5 % and 63.6% ± 20.2 % for CKC and fastICA, respectively, across different signal-to-noise ratios. The sensitivity and precision for MUs decomposed using the enhanced method remained at the same accuracy level (p <0.001) as those of normally decoded MUs. For the experimental signals, eight healthy subjects performed hand movements at five different force levels (10%-90%), during which sEMG signals were recorded and decomposed. The results indicate that the enhanced process increased the number of decoded MUs by 21.8% ± 10.9 % across all subjects. We discussed the possibility of fully capturing all activated motor units by appropriately reusing previously decoded MU filters and improving the balance of activated motor unit numbers across varying excitation levels.
Asunto(s)
Algoritmos , Electromiografía , Contracción Isométrica , Músculo Esquelético , Humanos , Contracción Isométrica/fisiología , Electromiografía/métodos , Músculo Esquelético/fisiología , Masculino , Neuronas Motoras/fisiología , Adulto , Potenciales de Acción/fisiología , Simulación por Computador , Antebrazo/fisiología , Femenino , Adulto Joven , Reclutamiento Neurofisiológico/fisiología , Procesamiento de Señales Asistido por ComputadorRESUMEN
Peripheral nerve injury (PNI) often leads to retrograde cell death in the spinal cord and dorsal root ganglia (DRG), hindering nerve regeneration and functional recovery. Repetitive magnetic stimulation (rMS) promotes nerve regeneration following PNI. Therefore, this study aimed to investigate the effects of rMS on post-injury neuronal death and nerve regeneration. Seventy-two rats underwent autologous sciatic nerve grafting and were divided into two groups: the rMS group, which received rMS and the control (CON) group, which received no treatment. Motor neuron, DRG neuron, and caspase-3 positive DRG neuron counts, as well as DRG mRNA expression analyses, were conducted at 1-, 4-, and 8-weeks post-injury. Functional and axon regeneration analyses were performed at 8-weeks post-injury. The CON group demonstrated a decreased DRG neuron count starting from 1 week post-injury, whereas the rMS group exhibited significantly higher DRG neuron counts at 1- and 4-weeks post-injury. At 8-weeks post-injury, the rMS group demonstrated a significantly greater myelinated nerve fiber density in autografted nerves. Furthermore, functional analysis showed significant improvements in latency and toe angle in the rMS group. Overall, these results suggest that rMS can prevent DRG neuron death and enhance nerve regeneration and motor function recovery after PNI.
Asunto(s)
Muerte Celular , Modelos Animales de Enfermedad , Ganglios Espinales , Regeneración Nerviosa , Traumatismos de los Nervios Periféricos , Nervio Ciático , Animales , Ganglios Espinales/metabolismo , Ratas , Nervio Ciático/lesiones , Traumatismos de los Nervios Periféricos/terapia , Masculino , Ratas Sprague-Dawley , Neuronas/metabolismo , Magnetoterapia/métodos , Recuperación de la Función , Neuronas Motoras/metabolismo , Neuronas Motoras/fisiologíaRESUMEN
Sarcopenia is a comprehensive degenerative disease with the progressive loss of skeletal muscle mass with age, accompanied by the loss of muscle strength and muscle dysfunction. Individuals with unmanaged sarcopenia may experience adverse outcomes. Periodically monitoring muscle function to detect muscle degeneration caused by sarcopenia and treating degenerated muscles is essential. We proposed a digital biomarker measurement technique using surface electromyography (sEMG) with electrical stimulation and wearable device to conveniently monitor muscle function at home. When motor neurons and muscle fibers are electrically stimulated, stimulated muscle contraction signals (SMCSs) can be obtained using an sEMG sensor. As motor neuron activation is important for muscle contraction and strength, their action potentials for electrical stimulation represent the muscle function. Thus, the SMCSs are closely related to muscle function, presumptively. Using the SMCSs data, a feature vector concatenating spectrogram-based features and deep learning features extracted from a convolutional neural network model using continuous wavelet transform images was used as the input to train a regression model for measuring the digital biomarker. To verify muscle function measurement technique, we recruited 98 healthy participants aged 20-60 years including 48 [49%] men who volunteered for this study. The Pearson correlation coefficient between the label and model estimates was 0.89, suggesting that the proposed model can robustly estimate the label using SMCSs, with mean error and standard deviation of -0.06 and 0.68, respectively. In conclusion, measuring muscle function using the proposed system that involves SMCSs is feasible.
Asunto(s)
Biomarcadores , Estimulación Eléctrica , Electromiografía , Contracción Muscular , Músculo Esquelético , Redes Neurales de la Computación , Dispositivos Electrónicos Vestibles , Humanos , Electromiografía/métodos , Masculino , Músculo Esquelético/fisiología , Contracción Muscular/fisiología , Adulto , Femenino , Algoritmos , Sarcopenia/fisiopatología , Sarcopenia/diagnóstico , Análisis de Ondículas , Persona de Mediana Edad , Aprendizaje Profundo , Neuronas Motoras/fisiología , Adulto Joven , Potenciales de Acción/fisiología , Voluntarios SanosRESUMEN
Homeostatic plasticity represents a set of mechanisms thought to stabilize some function of neural activity. Here, we identified the specific features of cellular or network activity that were maintained after the perturbation of GABAergic blockade in two different systems: mouse cortical neuronal cultures where GABA is inhibitory and motoneurons in the isolated embryonic chick spinal cord where GABA is excitatory (males and females combined in both systems). We conducted a comprehensive analysis of various spiking activity characteristics following GABAergic blockade. We observed significant variability in many features after blocking GABAA receptors (e.g., burst frequency, burst duration, overall spike frequency in culture). These results are consistent with the idea that neuronal networks achieve activity goals using different strategies (degeneracy). On the other hand, some features were consistently altered after receptor blockade in the spinal cord preparation (e.g., overall spike frequency). Regardless, these features did not express strong homeostatic recoveries when tracking individual preparations over time. One feature showed a consistent change and homeostatic recovery following GABAA receptor block. We found that spike rate within a burst (SRWB) increased after receptor block in both the spinal cord preparation and cortical cultures and then returned to baseline within hours. These changes in SRWB occurred at both single cell and population levels. Our findings indicate that the network prioritizes the burst spike rate, which appears to be a variable under tight homeostatic regulation. The result is consistent with the idea that networks can maintain an appropriate behavioral response in the face of challenges.
Asunto(s)
Potenciales de Acción , Homeostasis , Neuronas Motoras , Médula Espinal , Animales , Homeostasis/fisiología , Homeostasis/efectos de los fármacos , Médula Espinal/fisiología , Médula Espinal/efectos de los fármacos , Potenciales de Acción/fisiología , Potenciales de Acción/efectos de los fármacos , Femenino , Neuronas Motoras/fisiología , Neuronas Motoras/efectos de los fármacos , Ratones , Masculino , Células Cultivadas , Embrión de Pollo , Corteza Cerebral/fisiología , Corteza Cerebral/efectos de los fármacos , Antagonistas de Receptores de GABA-A/farmacología , Neuronas/fisiología , Neuronas/efectos de los fármacos , Receptores de GABA-A/metabolismo , Plasticidad Neuronal/fisiología , Plasticidad Neuronal/efectos de los fármacos , Ratones Endogámicos C57BLRESUMEN
Background: Spinal cord injury (SCI) results in lesions that destroy tissue and spinal tracts, leading to deficits in locomotor and autonomic function. We have previously shown that after SCI, surviving motoneurons innervating hindlimb muscles exhibit extensive dendritic atrophy, which can be attenuated by treadmill training or treatment with gonadal hormones post-injury. We have also shown that following SCI, both exercise and treatment with gonadal hormones improve urinary function. Animals exercised with forced running wheel training show improved urinary function as measured by bladder cystometry and sphincter electromyography, and treatment with gonadal hormones improves voiding patterns as measured by metabolic cage testing. Objective: The objective of the current study was to examine the potential protective effects of exercise or hormone treatment on the structure and function of motoneurons innervating the external urethral sphincter (EUS) after contusive SCI. Methods: Gonadally intact young adult male rats received either a sham or a thoracic contusion injury. Immediately after injury, one cohort of animals was implanted with subcutaneous Silastic capsules filled with estradiol (E) and dihydrotestosterone (D) or left blank; continuous hormone treatment occurred for 4 weeks post-injury. A separate cohort of SCI-animals received either 12 weeks of forced wheel running exercise or no exercise treatment starting two weeks after injury. At the end of treatment, urinary void volume was measured using metabolic cages and EUS motoneurons were labeled with cholera toxin-conjugated horseradish peroxidase, allowing for assessment of dendritic morphology in three dimensions. Results: Locomotor performance was improved in exercised animals after SCI. Void volumes increased after SCI in all animals; void volume was unaffected by treatment with exercise, but was dramatically improved by treatment with Eâ+âD. Similar to what we have previously reported for hindlimb motoneurons after SCI, dendritic length of EUS motoneurons was significantly decreased after SCI compared to sham animals. Exercise did not reverse injury-induced atrophy, however Eâ+âD treatment significantly protected dendritic length. Conclusions: These results suggest that some aspects of urinary dysfunction after SCI can be improved through treatment with gonadal hormones, potentially through their effects on EUS motoneurons. Moreover, a more comprehensive treatment regime that addresses multiple SCI-induced sequelae, i.e., locomotor and voiding deficits, would include both hormones and exercise.
Asunto(s)
Neuronas Motoras , Condicionamiento Físico Animal , Ratas Sprague-Dawley , Traumatismos de la Médula Espinal , Uretra , Micción , Animales , Traumatismos de la Médula Espinal/terapia , Traumatismos de la Médula Espinal/fisiopatología , Traumatismos de la Médula Espinal/patología , Neuronas Motoras/efectos de los fármacos , Neuronas Motoras/fisiología , Neuronas Motoras/patología , Masculino , Uretra/efectos de los fármacos , Uretra/patología , Micción/efectos de los fármacos , Micción/fisiología , Ratas , Condicionamiento Físico Animal/fisiología , Estradiol/farmacología , Modelos Animales de Enfermedad , Terapia por Ejercicio/métodosRESUMEN
OBJECTIVE: Motor Unit Number Estimation (MUNE) techniques are crucial in assessing lower motor neuron loss. MScanFit MUNE (MScanFit) is a novel tool which estimates MUNE values from compound muscle action potential (CMAP) scans by considering the probabilistic nature of motor unit firing. We conducted a prospective study to evaluate the diagnostic utility of MScanFit compared to quantitative electromyography (qEMG) in ALS patients. METHODS: We enrolled 35 patients diagnosed with amyotrophic lateral sclerosis (ALS) and 14 healthy controls, assessing qEMG and MScanFit MUNE in abductor pollicis brevis, abductor digiti minimi and tibialis anterior muscles. RESULTS: We found higher sensitivity of qEMG in detecting abnormalities compared to MScanFit, with a high concordance rate between the two techniques. Notably, a few muscles exhibited abnormal MUNE but normal qEMG findings, suggesting a potential complementary role for MScanFit in ALS diagnosis. Neurophysiological parameters from MScanFit showed good correlations with qEMG measures. Subclinical neurophysiological involvement was observed in muscles with normal strength, emphasizing the importance of sensitive diagnostic tools. CONCLUSION: MScanFit demonstrated validity in distinguishing ALS patients from healthy subjects and correlated well with qEMG parameters. SIGNIFICANCE: Our study confirmed the diagnostic utility of MScanFit MUNE in ALS, highlighting its role as a supplementary diagnostic tool.
Asunto(s)
Potenciales de Acción , Esclerosis Amiotrófica Lateral , Electromiografía , Neuronas Motoras , Músculo Esquelético , Humanos , Esclerosis Amiotrófica Lateral/fisiopatología , Esclerosis Amiotrófica Lateral/diagnóstico , Electromiografía/métodos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Estudios Prospectivos , Neuronas Motoras/fisiología , Potenciales de Acción/fisiología , Músculo Esquelético/fisiopatología , AdultoRESUMEN
Hyperexcitability of motor neurons and spinal cord motor circuitry has been widely reported in the early stages of Amyotrophic Lateral Sclerosis (ALS). Changes in the relative amount of excitatory to inhibitory inputs onto a neuron (E:I synaptic ratio), possibly through a developmental shift in synapse formation in favour of excitatory transmission, could underlie pathological hyperexcitability. Given that astrocytes play a major role in early synaptogenesis and are implicated in ALS pathogenesis, their potential contribution to disease mechanisms involving synaptic imbalances and subsequent hyperexcitability is also of great interest. In order to assess E:I ratios in ALS, we utilised a novel primary spinal neuron / astrocyte co-culture system, derived from neonatal mice, in which synapses are formed in vitro. Using multiple ALS mouse models we found that no combination of astrocyte or neuron genotype produced alterations in E:I synaptic ratios assessed using pre- and post-synaptic anatomical markers. Similarly, we observed that ephrin-B1, a major contact-dependent astrocytic synaptogenic protein, was not differentially expressed by ALS primary astrocytes. Further to this, analysis of E:I ratios across the entire grey matter of the lumbar spinal cord in young (post-natal day 16-19) ALS mice revealed no differences versus controls. Finally, analysis in co-cultures of human iPSC-derived motor neurons and astrocytes harbouring the pathogenic C9orf72 hexanucleotide repeat expansion showed no evidence of a bias toward excitatory versus inhibitory synapse formation. We therefore conclude, utilising multiple ALS models, that we do not observe significant changes in the relative abundance of excitatory versus inhibitory synapses as would be expected if imbalances in synaptic inputs contribute to early hyperexcitability.
Asunto(s)
Esclerosis Amiotrófica Lateral , Astrocitos , Técnicas de Cocultivo , Modelos Animales de Enfermedad , Neuronas Motoras , Médula Espinal , Sinapsis , Esclerosis Amiotrófica Lateral/patología , Esclerosis Amiotrófica Lateral/fisiopatología , Esclerosis Amiotrófica Lateral/metabolismo , Esclerosis Amiotrófica Lateral/genética , Animales , Astrocitos/metabolismo , Astrocitos/patología , Ratones , Sinapsis/metabolismo , Sinapsis/fisiología , Neuronas Motoras/metabolismo , Neuronas Motoras/patología , Neuronas Motoras/fisiología , Médula Espinal/metabolismo , Médula Espinal/patología , Humanos , Potenciales Postsinápticos Excitadores , Ratones Transgénicos , Células Cultivadas , Transmisión SinápticaRESUMEN
Axonal damage is a common feature of traumatic injury and neurodegenerative disease. The capacity for axons to regenerate and to recover functionality after injury is a phenomenon that is seen readily in the peripheral nervous system, especially in rodent models, but human axonal regeneration is limited and does not lead to full functional recovery. Here we describe a system where dynamics of human axonal outgrowth and regeneration can be evaluated via live imaging of human-induced pluripotent stem cell (hiPSC)-derived neurons cultured in microfluidic systems, in which cell bodies are isolated from their axons. This system could aid in studying axonal outgrowth dynamics and could be useful for testing potential drugs that encourage regeneration and repair of the nervous system.
Asunto(s)
Axones , Células Madre Pluripotentes Inducidas , Neuronas Motoras , Regeneración Nerviosa , Humanos , Células Madre Pluripotentes Inducidas/citología , Axones/fisiología , Neuronas Motoras/fisiología , Neuronas Motoras/citología , Regeneración Nerviosa/fisiología , Microfluídica/métodos , Microfluídica/instrumentación , Diferenciación Celular , Células Cultivadas , Dispositivos Laboratorio en un Chip , Técnicas Analíticas Microfluídicas/instrumentación , Técnicas Analíticas Microfluídicas/métodos , Técnicas de Cultivo de Célula/métodosRESUMEN
The protocol describes single-neuron ablation with a 2-photon laser system in the central nervous system (CNS) of intact Drosophila melanogaster larvae. Using this non-invasive method, the developing nervous system can be manipulated in a cell-specific manner. Disrupting the development of individual neurons in a network can be used to study how the nervous system can compensate for the loss of synaptic input. Individual neurons were specifically ablated in the giant fiber system of Drosophila, with a focus on two neurons: the presynaptic giant fiber (GF) and the postsynaptic tergotrochanteral motor neuron (TTMn). The GF synapses with the ipsilateral TTMn, which is crucial to the escape response. Ablating one of the GFs in the 3rd instar brain, just after the GF starts axonal growth, permanently removes the cell during the development of the CNS. The remaining GF reacts to the absent neighbor and forms an ectopic synaptic terminal to the contralateral TTMn. This atypical, bilaterally symmetric terminal innervates both TTMns, as demonstrated by dye coupling, and drives both motor neurons, as demonstrated by electrophysiological assays. In summary, the ablation of a single interneuron demonstrates synaptic competition between a bilateral pair of neurons that can compensate for the loss of one neuron and restore normal responses to the escape circuit.
Asunto(s)
Drosophila melanogaster , Larva , Neuronas Motoras , Sinapsis , Animales , Sinapsis/fisiología , Neuronas Motoras/citología , Neuronas Motoras/fisiología , Terapia por Láser/métodos , Sistema Nervioso Central/citología , Sistema Nervioso Central/fisiología , Neuronas/citología , Neuronas/fisiología , Técnicas de Ablación/métodosRESUMEN
The effectiveness of activated Ia afferents to discharge α-motoneurons is decreased during passive muscle lengthening compared with static and shortening muscle conditions. Evidence suggests that these regulations are explained by 1) greater postactivation depression induced by homosynaptic postactivation depression (HPAD) and 2) primary afferent depolarization (PAD). It remains uncertain whether muscle length impacts the muscle lengthening-related aspect of regulation of the effectiveness of activated Ia afferents to discharge α-motoneurons, HPAD, PAD, and heteronymous Ia facilitation (HF). We conducted a study involving 15 healthy young individuals. We recorded conditioned or nonconditioned soleus Hoffmann (H) reflex with electromyography (EMG) to estimate the effectiveness of activated Ia afferents to discharge α-motoneurons, HPAD, PAD, and HF during passive shortening, static, and lengthening muscle conditions at short, intermediate, and long lengths. Our results show that the decrease of effectiveness of activated Ia afferents to discharge α-motoneurons and increase of postactivation depression during passive muscle lengthening occur at all muscle lengths. For PAD and HF, we found that longer muscle length increases the magnitude of regulation related to muscle lengthening. To conclude, our findings support an inhibitory effect (resulting from increased postactivation depression) of muscle lengthening and longer muscle length on the effectiveness of activated Ia afferents to discharge α-motoneurons. The increase in postactivation depression associated with muscle lengthening can be attributed to the amplification of Ia afferents discharge.NEW & NOTEWORTHY Original results are that in response to passive muscle lengthening and increased muscle length, inhibition of the effectiveness of activated Ia afferents to discharge α-motoneurons increases, with primary afferent depolarization and homosynaptic postactivation depression mechanisms playing central roles in this regulatory process. Our findings highlight for the first time a cumulative inhibitory effect of muscle lengthening and increased muscle length on the effectiveness of activated Ia afferents to discharge α-motoneurons.