Neuromuscular junction

Summary

A neuromuscular junction (or myoneural junction) is a chemical synapse between a motor neuron and a muscle fiber. It allows the motor neuron to transmit a signal to the muscle fiber, causing muscle contraction. Muscles require innervation to function—and even just to maintain muscle tone, avoiding atrophy. In the neuromuscular system nerves from the central nervous system and the peripheral nervous system are linked and work together with muscles. Synaptic transmission at the neuromuscular junction begins when an action potential reaches the presynaptic terminal of a motor neuron, which activates voltage-gated calcium channels to allow calcium ions to enter the neuron. Calcium ions bind to sensor proteins (synaptotagmins) on synaptic vesicles, triggering vesicle fusion with the cell membrane and subsequent neurotransmitter release from the motor neuron into the synaptic cleft. In vertebrates, motor neurons release acetylcholine (ACh), a small molecule neurotransmitter, which diffu

Official source

https://en.wikipedia.org/wiki/Neuromuscular_junction

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Thymic epithelial cells (TECs) are organised in a unique 3D network that is critical for the development of efficient and self-tolerant T-cells. We report for the first time that the human thymus of all ages, even old and involuted, contains a significant number (up to 30%) of clonogenic TECs with extensive growth potential. All clonogenic TECs derive from a common EpCAM+ precursor, which within 48h in culture undergoes a molecular switch and gives rise to refringent EpCAM- colonies and stratified EpCAM+ colonies. The latter two subpopulations can be distinguished based on their morphology, their expression of genes implicated in epidermal stratification and their expression of genes implicated in epithelia-mesenchymal transition. Clonal analysis revealed that clonogenic cells are hierarchically organised, refringent cells being higher in the hierarchy than stratified cells. Although the thymus normally involutes with age, it can be the site of uncontrolled proliferation, resulting in the formation of thymic tumours including thymomas. Thymomas are classified by the WHO based on histological criteria as type A, B and AB and are frequently associated with Myasthenia Gravis, an autoimmune disease affecting the neuromuscular junction. The biology of thymomas is poorly understood, because of the rarity of the tumours and because of the lack of a reliable in vitro model. We report for the first time, that clonogenic cells can be isolated from all thymoma subtypes as well as from thymic hyperplasia and mediastinal teratoma. The latter cells displayed many similarities with normal TECs but also differences in terms of morphology, gene expression and genetic profile. Importantly, all thymic tumours studied contained refringent-like EpCAM- cells and stratified EpCAM+ cells, supporting the hypothesis that thymic tumour-initiating cells arise from clonogenic TECs. We have not succeeded yet in developing an appropriate assay to support the growth of clonogenic epithelial cells from thymic tumours in vivo. Finally, we report that the SY5 monoclonal antibody raised against human involucrin reproducibly cross-reacts with a molecule present in the Golgi apparatus of refringent cells derived from normal and pathological thymi. Immunocytochemistry and knock-down experiments revealed that the latter molecule is not involucrin. Epitope mapping by phage-display experiments and data base search identified putative candidate proteins, including nesprin-1, a player of the neuromuscular junction, which could be the key to understand the frequent association of thymomas with Myasthenia Gravis.

EPFL2017

Combining a 3D Reflex Based Neuromuscular Model with a State Estimator Based on Central Pattern Generators

Tycho Jan Henricus Brug, Florin Dzeladini, Auke Ijspeert, Amy Roning Wu

A neuromuscular model (NMC) presented by H. Geyer and extended by S. Song shows very interesting similarities with real human locomotion. The model uses a combination of reflex loops to generate stable locomotion and is able to cope with external disturbances and adapt to different conditions. However, to our knowledge no works exist on the capability of the model to handle sensory noise. In this paper, we present a method for designing Central Pattern Generators (CPG) as feedback predictors, which can be used to handle large amount of sensory noise. We show that the whole system (NMC + CPG) is able to cope with a very large amount of noise, much larger than what the original system (NMC) could handle.

Springer International Publishing Ag2017

An Adaptive Neuromuscular Controller for Assistive Lower-Limb Exoskeletons: A Preliminary Study on Subjects with Spinal Cord Injury

Tycho Jan Henricus Brug, Florin Dzeladini, Auke Ijspeert, Amy Roning Wu

Versatility is important for a wearable exoskeleton controller to be responsive to both the user and the environment. These characteristics are especially important for subjects with spinal cord injury (SCI), where active recruitment of their own neuromuscular system could promote motor recovery. Here we demonstrate the capability of a novel, biologically-inspired neuromuscular controller (NMC) which uses dynamical models of lower limb muscles to assist the gait of SCI subjects. Advantages of this controller include robustness, modularity, and adaptability. The controller requires very few inputs (i.e., joint angles, stance, and swing detection), can be decomposed into relevant control modules (e.g., only knee or hip control), and can generate walking at different speeds and terrains in simulation. We performed a preliminary evaluation of this controller on a lower-limb knee and hip robotic gait trainer with seven subjects (N = 7, four with complete paraplegia, two incomplete, one healthy) to determine if the NMC could enable normal-like walking. During the experiment, SCI subjects walked with body weight support on a treadmill and could use the handrails. With controller assistance, subjects were able to walk at fast walking speeds for ambulatory SCI subjects-from 0.6 to 1.4 m/s. Measured joint angles and NMC-provided joint torques agreed reasonably well with kinematics and biological joint torques of a healthy subject in shod walking. Some differences were found between the torques, such as the lack of knee flexion near mid-stance, but joint angle trajectories did not seem greatly affected. The NMC also adjusted its torque output to provide more joint work at faster speeds and thus greater joint angles and step length. We also found that the optimal speed-step length curve observed in healthy humans emerged for most of the subjects, albeit with relatively longer step length at faster speeds. Therefore, with very few sensors and no predefined settings for multiple walking speeds or adjustments for subjects of differing anthropometry and walking ability, NMC enabled SCI subjects to walk at several speeds, including near healthy speeds, in a healthy-like manner. These preliminary results are promising for future implementation of neuromuscular controllers on wearable prototypes for real-world walking conditions.

Frontiers Research Foundation2017

EPFL2017

An Adaptive Neuromuscular Controller for Assistive Lower-Limb Exoskeletons: A Preliminary Study on Subjects with Spinal Cord Injury

Tycho Jan Henricus Brug, Florin Dzeladini, Auke Ijspeert, Amy Roning Wu

Frontiers Research Foundation2017