-
Annual Review of Neuroscience 2010Although often considered as a group, spinal motor neurons are highly diverse in terms of their morphology, connectivity, and functional properties and differ... (Comparative Study)
Comparative Study Review
Although often considered as a group, spinal motor neurons are highly diverse in terms of their morphology, connectivity, and functional properties and differ significantly in their response to disease. Recent studies of motor neuron diversity have clarified developmental mechanisms and provided novel insights into neurodegeneration in amyotrophic lateral sclerosis (ALS). Motor neurons of different classes and subtypes--fast/slow, alpha/gamma--are grouped together into motor pools, each of which innervates a single skeletal muscle. Distinct mechanisms regulate their development. For example, glial cell line-derived neurotrophic factor (GDNF) has effects that are pool-specific on motor neuron connectivity, column-specific on axonal growth, and subtype-specific on survival. In multiple degenerative contexts including ALS, spinal muscular atrophy (SMA), and aging, fast-fatigable (FF) motor units degenerate early, whereas motor neurons innervating slow muscles and those involved in eye movement and pelvic sphincter control are strikingly preserved. Extrinsic and intrinsic mechanisms that confer resistance represent promising therapeutic targets in these currently incurable diseases.
Topics: Animals; Cell Differentiation; Humans; Motor Neuron Disease; Motor Neurons
PubMed: 20367447
DOI: 10.1146/annurev.neuro.051508.135722 -
Handbook of Clinical Neurology 2023This chapter considers the principles that underlie neurophysiological studies of upper motor neuron or lower motor neuron lesions, based on an understanding of the... (Review)
Review
This chapter considers the principles that underlie neurophysiological studies of upper motor neuron or lower motor neuron lesions, based on an understanding of the normal structure and function of the motor system. Human motor neurophysiology consists of an evaluation of the active components of the motor system that are relevant to volitional movements. Relatively primitive motor skills include locomotion, much dependent on the spinal cord central pattern generator, reaching, involving proximal and distal muscles activation, and grasping. Humans are well prepared to perform complex movements like writing. The role of motor cortex is critical for the motor activity, very dependent on the continuous sensory feedback, and this is essential for adapting the force and speed control, which contributes to motor learning. Most corticospinal neurons in the brain project to brainstem and spinal cord, many with polysynaptic inhibitory rather than excitatory connections. The monosynaptic connections observed in humans and primates constitute a specialized pathway implicated in fractional finger movements. Spinal cord has a complex physiology, and local reflexes and sensory feedback are essential to control adapted muscular contraction during movement. The cerebellum has a major role in motor coordination, but also consistent roles in sensory activities, speech, and language, in motor and spatial memory, and in psychological activity. The motor unit is the final effector of the motor drive. The complex interplay between the lower motor neuron, its axon, motor end-plates, and muscle fibers allows a relevant plasticity in the movement output.
Topics: Animals; Humans; Neurophysiology; Spinal Cord; Motor Neurons; Spinal Cord Injuries; Motor Cortex
PubMed: 37562869
DOI: 10.1016/B978-0-323-98818-6.00018-2 -
Seminars in Cell & Developmental Biology Jan 2019Motor neurons differentiate from progenitor cells and cluster as motor nuclei, settling next to the floor plate in the brain stem and spinal cord. Although precise... (Review)
Review
Motor neurons differentiate from progenitor cells and cluster as motor nuclei, settling next to the floor plate in the brain stem and spinal cord. Although precise positioning of motor neurons is critical for their functional input and output, the molecular mechanisms that guide motor neurons to their proper positions remain poorly understood. Here, we review recent evidence of motor neuron positioning mechanisms, highlighting situations in which motor neuron cell bodies can migrate, and experiments that show that their migration is regulated by axon guidance cues. The view that emerges is that motor neurons are actively trapped or restricted in static positions, as the cells balance a push in the dorsal direction by repulsive Slit/Robo cues and a pull in the ventral direction by attractive Netrin-1/DCC cues. These new functions of guidance cues are necessary fine-tuning to set up patterns of motor neurons at their proper positions in the neural tube during embryogenesis.
Topics: Axon Guidance; Cell Movement; Motor Neurons; Neurogenesis
PubMed: 29141180
DOI: 10.1016/j.semcdb.2017.11.016 -
International Journal of Molecular... Aug 2021Motor neuron disease (MND) comprises a group of fatal neurodegenerative diseases with no effective cure. As progressive motor neuron cell death is one of pathological... (Review)
Review
Motor neuron disease (MND) comprises a group of fatal neurodegenerative diseases with no effective cure. As progressive motor neuron cell death is one of pathological characteristics of MND, molecules which protect these cells are attractive therapeutic targets. Accumulating evidence indicates that EphA4 activation is involved in MND pathogenesis, and inhibition of EphA4 improves functional outcomes. However, the underlying mechanism of EphA4's function in MND is unclear. In this review, we first present results to demonstrate that EphA4 signalling acts directly on motor neurons to cause cell death. We then review the three most likely mechanisms underlying this effect.
Topics: Animals; Cell Death; Humans; Motor Neuron Disease; Motor Neurons; Receptor, EphA4; Signal Transduction
PubMed: 34502339
DOI: 10.3390/ijms22179430 -
Histology and Histopathology Nov 2017Amyotrophic lateral sclerosis (ALS) is typically defined by a loss of motor neurons in the central nervous system. Accordingly, morphological analysis for decades... (Review)
Review
Amyotrophic lateral sclerosis (ALS) is typically defined by a loss of motor neurons in the central nervous system. Accordingly, morphological analysis for decades considered motor neurons (in the cortex, brainstem and spinal cord) as the neuronal population selectively involved in ALS. Similarly, this was considered the pathological marker to score disease severity ex vivo both in patients and experimental models. However, the concept of non-autonomous motor neuron death was used recently to indicate the need for additional cell types to produce motor neuron death in ALS. This means that motor neuron loss occurs only when they are connected with other cell types. This concept originally emphasized the need for resident glia as well as non-resident inflammatory cells. Nowadays, the additional role of neurons other than motor neurons emerged in the scenario to induce non-autonomous motor neuron death. In fact, in ALS neurons diverse from motor neurons are involved. These cells play multiple roles in ALS: (i) they participate in the chain of events to produce motor neuron loss; (ii) they may even degenerate more than and before motor neurons. In the present manuscript evidence about multi-neuronal involvement in ALS patients and experimental models is discussed. Specific sub-classes of neurons in the whole spinal cord are reported either to degenerate or to trigger neuronal degeneration, thus portraying ALS as a whole spinal cord disorder rather than a disease affecting motor neurons solely. This is associated with a novel concept in motor neuron disease which recruits abnormal mechanisms of cell to cell communication.
Topics: Amyotrophic Lateral Sclerosis; Animals; Humans; Motor Neuron Disease; Motor Neurons; Nerve Degeneration; Neurons; Spinal Cord
PubMed: 28397197
DOI: 10.14670/HH-11-895 -
Nature Neuroscience Apr 2016Directing the differentiation of induced pluripotent stem cells into motor neurons has allowed investigators to develop new models of amyotrophic lateral sclerosis... (Review)
Review
Directing the differentiation of induced pluripotent stem cells into motor neurons has allowed investigators to develop new models of amyotrophic lateral sclerosis (ALS). However, techniques vary between laboratories and the cells do not appear to mature into fully functional adult motor neurons. Here we discuss common developmental principles of both lower and upper motor neuron development that have led to specific derivation techniques. We then suggest how these motor neurons may be matured further either through direct expression or administration of specific factors or coculture approaches with other tissues. Ultimately, through a greater understanding of motor neuron biology, it will be possible to establish more reliable models of ALS. These in turn will have a greater chance of validating new drugs that may be effective for the disease.
Topics: Amyotrophic Lateral Sclerosis; Animals; Cell Differentiation; Cells, Cultured; Coculture Techniques; Humans; Induced Pluripotent Stem Cells; Motor Neurons
PubMed: 27021939
DOI: 10.1038/nn.4273 -
Journal of the Neurological Sciences May 2021
Topics: Benchmarking; Humans; Motor Neurons; Nerve Degeneration; Poliomyelitis; Survivors
PubMed: 33810879
DOI: 10.1016/j.jns.2021.117360 -
Clinical Neurophysiology : Official... Jul 2016In the motor system there is a complex interplay between cortical structures and spinal cord lower motor neurons (LMN). In this system both inhibitory and excitatory... (Review)
Review
In the motor system there is a complex interplay between cortical structures and spinal cord lower motor neurons (LMN). In this system both inhibitory and excitatory neurons have relevant roles. LMN loss is a marker of motor neuron disease/amyotrophic lateral sclerosis (MND/ALS). Conventional needle electromyography (EMG) does not allow LMN loss to be quantified. Measurement of compound muscle action potential (CMAP) amplitude or area, and the neurophysiological index, provide a surrogate estimate of the number of functional motor units. Increased motor neuronal excitability is a neurophysiological marker of ALS in the context of a suspected clinical and electrophysiological diagnosis. In the LMN system, fasciculation potentials (FPs) are the earliest changes observed in affected muscles, a feature of LMN hyperexcitability. Reinnervation is best investigated by needle EMG although other methods can be explored. Moreover needle EMG give information about the temporal profile of the reinnervation process, important ancillary data. Quantitative motor unit potential analysis is a valuable method of evaluating reinnervation. The importance of FPs has been recognized in the Awaji criteria for the electrodiagnosis of ALS, criteria that are a sensitive adjunct to the revised El Escorial criteria. Finally, functionality of LMN's, and perhaps excitability studies in motor nerves, aids understanding of the disease process, allowing measurement of potential treatment effects in clinical trials. Other investigational techniques, such as electrical impedance myography, muscle and nerve ultrasound, and spinal cord imaging methods may prove useful in future.
Topics: Amyotrophic Lateral Sclerosis; Electromyography; Humans; Motor Neurons; Muscle, Skeletal; Neural Conduction
PubMed: 27117334
DOI: 10.1016/j.clinph.2016.03.024 -
The Journal of Experimental Biology Aug 2019Motor behaviors depend on neural signals in the brain. Regardless of where in the brain behavior patterns arise, the central nervous system sends projections to motor... (Review)
Review
Motor behaviors depend on neural signals in the brain. Regardless of where in the brain behavior patterns arise, the central nervous system sends projections to motor neurons, which in turn project to and control temporally appropriate muscle contractions; thus, motor neurons are traditionally considered the last relay from the central nervous system to muscles. However, in an array of species and motor systems, an accumulating body of evidence supports a more complex role of motor neurons in pattern generation. These studies suggest that motor neurons not only relay motor patterns to the periphery, but directly contribute to pattern generation by providing feedback to upstream circuitry. In spinal and hindbrain circuits in a variety of animals - including flies, worms, leeches, crustaceans, rodents, birds, fish, amphibians and mammals - studies have indicated a crucial role for motor neuron feedback in maintaining normal behavior patterns dictated by the activity of a central pattern generator. Hence, in this Review, we discuss literature examining the role of motor neuron feedback across many taxa and behaviors, and set out to determine the prevalence of motor neuron participation in motor circuits.
Topics: Animals; Central Pattern Generators; Feedback, Physiological; Invertebrates; Motor Neurons; Vertebrates
PubMed: 31420449
DOI: 10.1242/jeb.193318 -
Current Opinion in Neurobiology Dec 2018The embryonic generation of motor neurons is a complex process involving progenitor patterning, fate specification, differentiation, and maturation. Throughout this... (Review)
Review
The embryonic generation of motor neurons is a complex process involving progenitor patterning, fate specification, differentiation, and maturation. Throughout this progression, the differential expression of transcription factors has served as our road map for the eventual cell fate of nascent motor neurons. Recent findings from in vivo and in vitro models of motor neuron development have expanded our understanding of how transcription factors govern motor neuron identity and their individual regulatory mechanisms. With the advent of next generation sequencing approaches, researchers now have unprecedented access to the gene regulatory dynamics involved in motor neuron development and are uncovering new connections linking neurodevelopment and neurodegenerative disease.
Topics: Animals; Cell Differentiation; Gene Expression Regulation, Developmental; Motor Neurons; Transcription Factors
PubMed: 29694927
DOI: 10.1016/j.conb.2018.04.012