scholarly journals Reduced Endplate Currents Underlie Motor Unit Dysfunction in Canine Motor Neuron Disease

2002 ◽  
Vol 88 (6) ◽  
pp. 3293-3304 ◽  
Author(s):  
Mark M. Rich ◽  
Robert. F. Waldeck ◽  
Linda C. Cork ◽  
Rita J. Balice-Gordon ◽  
Robert E. W. Fyffe ◽  
...  
Keyword(s):  
Motor Neuron ◽  
Motor Neuron Disease ◽  
Motor Unit ◽  
Conduction Velocity ◽  
Motor Neurons ◽  
Muscle Fiber ◽  
Muscular Atrophy ◽  
Motor Units ◽  
Postnatal Maturation ◽  
Axonal Conduction

Hereditary canine spinal muscular atrophy (HCSMA) is an autosomal dominant degenerative disorder of motor neurons. In homozygous animals, motor units produce decreased force output and fail during repetitive activity. Previous studies suggest that decreased efficacy of neuromuscular transmission underlies these abnormalities. To examine this, we recorded muscle fiber endplate currents (EPCs) and found reduced amplitudes and increased failures during nerve stimulation in homozygotes compared with wild-type controls. Comparison of EPC amplitudes with muscle fiber current thresholds indicate that many EPCs from homozygotes fall below threshold for activating muscle fibers but can be raised above threshold following potentiation. To determine whether axonal abnormalities might play a role in causing motor unit dysfunction, we examined the postnatal maturation of axonal conduction velocity in relation to the appearance of tetanic failure. We also examined intracellularly labeled motor neurons for evidence of axonal neurofilament accumulations, which are found in many instances of motor neuron disease including HCSMA. Despite the appearance of tetanic failure between 90 and 120 days, average motor axon conduction velocity increased with age in homozygotes and achieved adult levels. Normal correlations between motor neuron properties (including conduction velocity) and motor unit properties were also observed. Labeled proximal motor axons of several motor neurons that supplied failing motor units exhibited little or no evidence of axonal swellings. We conclude that decreased release of transmitter from motor terminals underlies motor unit dysfunction in HCSMA and that the mechanisms determining the maturation of axonal conduction velocity and the pattern of correlation between motor neuron and motor unit properties do not contribute to the appearance or evolution of motor unit dysfunction.

Motor-unit properties following cross-reinnervation of cat lateral gastrocnemius and soleus muscles with medial gastrocnemius nerve. II. Influence of muscle on motoneurons

1987 ◽  
Vol 57 (4) ◽  
pp. 1227-1245 ◽  
Author(s):  
R. C. Foehring ◽  
G. W. Sypert ◽  
J. B. Munson
Keyword(s):  
Electrical Properties ◽  
Motor Unit ◽  
Conduction Velocity ◽  
Decay Time ◽  
Motor Units ◽  
Input Resistance ◽  
Medial Gastrocnemius ◽  
Lateral Gastrocnemius ◽  
Mean Values ◽  
Axonal Conduction

We tested whether the muscle innervated may influence the expression of motoneuron electrical properties. Properties of individual motor units were examined following cross-reinnervation (X-reinnervation) of cat lateral gastrocnemius (LG) and soleus muscles by the medial gastrocnemius (MG) nerve. We examined animals at two postoperative times: 9-10 wk (medX) and 9-11 mo (longX). For comparison, normal LG and soleus motoneuron properties were also studied. Motor units were classified on the basis of their contractile responses as fast contracting fatigable, fast intermediate fast contracting fatigue resistant, and slow types FF, FI, FR, or S, respectively) (9, 21). Motoneuron electrical properties (rheobase, input resistance, axonal conduction velocity, afterhyperpolarization) were measured. After 9-11 mo, MG motoneurons that innervated LG muscle showed recovery of electrical properties similar to self-regenerated MG motoneurons. The relationships between motoneuron electrical properties were largely similar to self-regenerated MG. For MG motoneurons that innervated LG, motoneuron type (65) predicted motor-unit type in 74% of cases. LongX-soleus motoneurons differed from longX-LG motoneurons or self-regenerated MG motoneurons in mean values for motoneuron electrical properties. The differences in overall means reflected the predominance of type S motor units. The relationships between motoneuron electrical properties were also different than in self-regenerated MG motoneurons. In all cases, the alterations were in the direction of properties of type S units, and the relationship between normal soleus motoneurons and their muscle units. Within motor-unit types, the mean values were typical for that type in self-regenerated MG. Motoneuron type (65) was a fairly strong predictor of motor-unit type in longX soleus. MG motoneurons that innervated soleus displayed altered values for axonal conduction velocity, rheobase, and input resistance, which could indicate incomplete recovery from the axotomized state. However, although mean afterhyperpolarization (AHP) half-decay time was unaltered by axotomy (25), this parameter was significantly lengthened in MG motoneurons that innervated soleus muscle. There were, however, individual motoneuron-muscle-unit mismatches, which suggested that longer mean AHP half-decay time may also be due to incomplete recovery of a subpopulation of motoneurons. Those MG motoneurons able to specify soleus muscle-fiber type exhibited motoneuron electrical properties typical of that same motoneuron type in self-regenerated MG.(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals Activity-Driven Synaptic and Axonal Degeneration in Canine Motor Neuron Disease

2004 ◽  
Vol 92 (2) ◽  
pp. 1175-1181 ◽  
Author(s):  
Dario I. Carrasco ◽  
Mark M. Rich ◽  
Qingbo Wang ◽  
Timothy C. Cope ◽  
Martin J. Pinter
Keyword(s):  
Motor Neuron ◽  
Motor Neuron Disease ◽  
Motor Unit ◽  
Neuromuscular Junctions ◽  
Muscular Atrophy ◽  
Motor Axon ◽  
Medial Gastrocnemius ◽  
Neuron Activity ◽  
Functional Changes ◽  
Unit Function

The role of neuronal activity in the pathogenesis of neurodegenerative disease is largely unknown. In this study, we examined the effects of increasing motor neuron activity on the pathogenesis of a canine version of inherited motor neuron disease (hereditary canine spinal muscular atrophy). Activity of motor neurons innervating the ankle extensor muscle medial gastrocnemius (MG) was increased by denervating close synergist muscles. In affected animals, 4 wk of synergist denervation accelerated loss of motor-unit function relative to control muscles and decreased motor axon conduction velocities. Slowing of axon conduction was greatest in the most distal portions of motor axons. Morphological analysis of neuromuscular junctions (NMJs) showed that these functional changes were associated with increased loss of intact innervation and with the appearance of significant motor axon and motor terminal sprouting. These effects were not observed in the MG muscles of age-matched, normal animals with synergist denervation for 5 wk. The results indicate that motor neuron action potential activity is a major contributing factor to the loss of motor-unit function and degeneration in inherited canine motor neuron disease.

scholarly journals Motor neuron disease presenting with fetal akinesia

2018 ◽  
Vol 45 (S1) ◽  
pp. S4-S4
Author(s):  
P. Shannon ◽  
D. Chitayat ◽  
K. Chong ◽  
C. Dunham ◽  
C. Fallet-Bianco
Keyword(s):  
Motor Neuron ◽  
Motor Neuron Disease ◽  
Globus Pallidus ◽  
Motor Neurons ◽  
Muscular Atrophy ◽  
Neuronal Loss ◽  
Ischemic Injury ◽  
Neuroaxonal Dystrophy ◽  
Lysosomal Storage ◽  
Whole Exome

By contrast to infantile spinal muscular atrophy, which usually links to deletions in the SMN genes, fetal onset motor neuron disease is poorly reported. We collected a series of twelve cases of fetal arthrogryposis (16-31 weeks gestational age) with fetal motor neuron disease and excluded infectious diseases, lysosomal storage disease and neuroaxonal dystrophy. Of these twelve, 3 were thought to be ischemic in nature with microvascular alterations and systemic or central nervous system ischemic injury. The remaining 9 all displayed marked reduction in anterior horn motor neurons. Of these 9, four demonstrated mineralised neurons, four demonstrated either neuronal loss or cavitation in the globus pallidus, and in two, degenerating neurons were detectable in the brainstem or globus pallidus. Specific sequencing of SMN1 was performed in 6 of 9 and was reported as normal. Whole exome sequencing was performed in 4 without definitive diagnosis. We conclude that fetal motor neuron disease can be distinguished from ischemic injury, is morphologically heterogeneous, may affect the globus pallidus and is rarely linked to SMN1 mutations.

Spike-triggered average torque and muscle fiber conduction velocity of low-threshold motor units following submaximal endurance contractions

2005 ◽  
Vol 98 (4) ◽  
pp. 1495-1502 ◽  
Author(s):  
Dario Farina ◽  
Lars Arendt-Nielsen ◽  
Thomas Graven-Nielsen
Keyword(s):  
Action Potential ◽  
Motor Unit ◽  
Conduction Velocity ◽  
Surface Potential ◽  
Muscle Fiber ◽  
Discharge Rate ◽  
Motor Units ◽  
Muscle Fiber Conduction Velocity ◽  
Sustained Contraction ◽  
Low Threshold

The motor unit twitch torque is modified by sustained contraction, but the association to changes in muscle fiber electrophysiological properties is not fully known. Thus twitch torque, muscle fiber conduction velocity, and action potential properties of single motor units were assessed in 11 subjects following an isometric submaximal contraction of the tibialis anterior muscle until endurance. The volunteers activated a target motor unit at the minimum discharge rate in eight 3-min-long contractions, three before and five after an isometric contraction at 40% of the maximal torque, sustained until endurance. Multichannel surface electromyogram signals and joint torque were averaged with the target motor unit potential as trigger. Discharge rate (mean ± SE, 6.6 ± 0.2 pulses/s) and interpulse interval variability (33.3 ± 7.0%) were not different in the eight contractions. Peak twitch torque and recruitment threshold increased significantly (93 ± 29 and 12 ± 5%, P < 0.05) in the contraction immediately after the endurance task with respect to the preendurance values (0.94 ± 0.26 mN·m and 3.7 ± 0.5% of the maximal torque), whereas time to peak of the twitch torque did not change (74.4 ± 10.1 ms). Muscle fiber conduction velocity decreased and action potential duration increased in the contraction after the endurance (6.3 ± 1.8 and 9.8 ± 1.8%, respectively, P < 0.05; preendurance values, 3.9 ± 0.2 m/s and 11.1 ± 0.8 ms), whereas the surface potential peak-to-peak amplitude did not change (27.1 ± 3.1 μV). There was no significant correlation between the relative changes in muscle fiber conduction velocity or surface potential duration and in peak twitch torque ( R2 = 0.04 and 0.10, respectively). In conclusion, modifications in peak twitch torque of low-threshold motor units with sustained contraction are mainly determined by mechanisms not related to changes in action potential shape and in its propagation velocity.

Motor neuron disease

2018 ◽  
Author(s):  
Martin R. Turner
Keyword(s):  
Motor Neuron ◽  
Motor Neuron Disease ◽  
Motor Neurons ◽  
Corticospinal Tract ◽  
Muscular Atrophy ◽  
Muscle Denervation ◽  
Genetic Overlap ◽  
Upper Motor Neurons ◽  
Primary Lateral ◽  
Lateral Sclerosis

Motor neuron disease (MND) is characterized by progressive muscular weakness due to simultaneous degeneration of lower and upper motor neurons (L/UMNs). Involvement of LMNs, arising from the anterior horns of the spinal cord and brainstem, leads to secondary wasting as a result of muscle denervation. Involvement of the UMNs of the motor cortex and corticospinal tract results in spasticity. In ~85% of cases, there is clear clinical involvement of both, and the condition is termed ‘amyotrophic lateral sclerosis’ (ALS; a term often used synonymously with MND). In ~13% of cases, there may be only LMN signs apparent, in which case the condition is termed ‘progressive muscular atrophy’, although such cases have a natural history that is to largely identical to that of ALS. In a very small group of patients (~2%), there are only UMN signs for at least the first 4 years, in which case the condition is termed ‘primary lateral sclerosis’; such cases have a uniformly slower progression. There is clinical, neuropathological, and genetic overlap between MND and some forms of frontotemporal dementia.

scholarly journals Adjustments Differ Among Low-Threshold Motor Units During Intermittent, Isometric Contractions

2009 ◽  
Vol 101 (1) ◽  
pp. 350-359 ◽  
Author(s):  
Dario Farina ◽  
Aleš Holobar ◽  
Marco Gazzoni ◽  
Damjan Zazula ◽  
Roberto Merletti ◽  
...  
Keyword(s):  
Motor Unit ◽  
Conduction Velocity ◽  
Muscle Fiber ◽  
Discharge Rate ◽  
Motor Units ◽  
Abductor Pollicis Brevis ◽  
Muscle Fiber Conduction Velocity ◽  
Neuron Activation ◽  
Active Motor ◽  
Low Threshold

We investigated the changes in muscle fiber conduction velocity, recruitment and derecruitment thresholds, and discharge rate of low-threshold motor units during a series of ramp contractions. The aim was to compare the adjustments in motor unit activity relative to the duration that each motor unit was active during the task. Multichannel surface electromyographic (EMG) signals were recorded from the abductor pollicis brevis muscle of eight healthy men during 12-s contractions ( n = 25) in which the force increased and decreased linearly from 0 to 10% of the maximum. The maximal force exhibited a modest decline (8.5 ± 9.3%; P < 0.05) at the end of the task. The discharge times of 73 motor units that were active for 16–98% of the time during the first five contractions were identified throughout the task by decomposition of the EMG signals. Action potential conduction velocity decreased during the task by a greater amount for motor units that were initially active for >70% of the time compared with that of less active motor units. Moreover, recruitment and derecruitment thresholds increased for these most active motor units, whereas the thresholds decreased for the less active motor units. Another 18 motor units were recruited at an average of 171 ± 32 s after the beginning of the task. The recruitment and derecruitment thresholds of these units decreased during the task, but muscle fiber conduction velocity did not change. These results indicate that low-threshold motor units exhibit individual adjustments in muscle fiber conduction velocity and motor neuron activation that depended on the relative duration of activity during intermittent contractions.

scholarly journals Hereditary Canine Spinal Muscular Atrophy: An Animal Model of Motor Neuron Disease

1991 ◽  
Vol 18 (S3) ◽  
pp. 432-434 ◽  
Author(s):  
Linda C. Cork
Keyword(s):  
Spinal Muscular Atrophy ◽  
Motor Neuron ◽  
Motor Neuron Disease ◽  
Motor Neurons ◽  
Autosomal Dominant ◽  
Muscular Atrophy ◽  
Canine Model ◽  
Therapeutic Interventions ◽  
Motor Neuron Diseases ◽  
Human Motor

ABSTRACT:Motor neuron diseases selectively produce degeneration and death of motor neurons; the pathogenesis of these disorders and the specificity for this population of neurons are unknown. Hereditary Canine Spinal Muscular Atrophy produces a lower motor neuron disease which is clinically and pathologically similar to human motor neuron disease: motor neurons dysfunction and degenerate. The canine model provides an opportunity to investigate early stages of disease when there are viable motor neurons still present and might be responsive to a variety of therapeutic interventions. The canine disease, like the human disease, is inherited as an autosomal dominant. The extensive canine pedigree of more than 200 characterized individuals permits genetic analysis using syntenic linkage techniques which may identify a marker for the canine trait and provide insights into homologous regions for study in human kindreds.

Types of Motor Neuron Diseases

2017 ◽  
Author(s):  
Nimish Thakore ◽  
Erik P Pioro
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Spinal Muscular Atrophy ◽  
Motor Neuron ◽  
Motor Neuron Disease ◽  
Motor Neurons ◽  
Muscular Atrophy ◽  
Motor Neuron Diseases ◽  
The Subject ◽  
Upper Motor Neurons ◽  
Lateral Sclerosis

Disorders of lower motor neurons (LMNs, or anterior horn cells) and upper motor neurons (UMNs), jointly termed motor neuron disorders (MNDs), are diverse and numerous. The prototypical MND, namely amyotrophic lateral sclerosis (ALS), a relentlessly progressive lethal disorder of adults, is the subject of another section and will not be discussed further here. Other MNDs include spinal muscular atrophy (SMA), of which there are four types: Kennedy’s disease, Brown-Violetto-Van Laere, and Fazio-Londe syndromes, lower motor neuron disorders as part of neurodegenerations and secondary motor neuron disease as part of malignancy, radiation and infection.

Relationship among recruitment order, axonal conduction velocity, and muscle-unit properties of type-identified motor units in cat plantaris muscle

1985 ◽  
Vol 53 (5) ◽  
pp. 1303-1322 ◽  
Author(s):  
F. E. Zajac ◽  
J. S. Faden
Keyword(s):  
Motor Unit ◽  
Conduction Velocity ◽  
Motor Units ◽  
Motor Axon ◽  
Monosynaptic Reflex ◽  
Axonal Conduction ◽  
Group I ◽  
Recruitment Order ◽  
Fast Twitch ◽  
Tetanic Tension

A strict interpretation of the size-principle hypothesis (37, 39-41) is that a muscle's motor units should be recruited in an ascending order according to both the size of their motoneurons and the size of their innervated muscle units (for reviews see Refs. 9, 39, 73). Studies of large mixed muscles in the cat hindlimb, however, have shown that motor axonal conduction velocity and tetanic tension, which are frequently considered indices of motoneuron and muscle-unit size, respectively, are uncorrelated in the fast-twitch (type F) motor-unit subpopulation (12, 13, 23, 24, 30, 32, 63, 71, 79). Attempting to focus on type F units, we compared the recruitment order of 42 pairs of cat plantaris (PL) motor units with both axonal conduction velocity and tetanic tension as well as with other muscle-unit properties. Single PL alpha-motor axons were functionally isolated in intact L7 ventral root filaments of decerebrate cats. Tension responses produced by stimulating each isolated motor axon were used to find the tetanic tension of the muscle unit and to classify the unit (12) as either type S (slow twitch, fatigue resistant), type FR (fast twitch, fatigue resistant), type FI (fast twitch, intermediate fatigability), or type FF (fast twitch, highly fatigable). Conduction velocity of each isolated axon was computed from measurements of axonal conduction time and length. The axon's reflex discharges were recorded from the proximal end of the cut filament and compared with the discharges of another PL axon residing in a different, previously cut filament of the same cat. The recruitment order of each motor-unit pair studied was found during reflexes elicited by homonymous muscle stretch, tendon taps, or single shocks at group I intensity to the PL nerve. If either axon of the pair failed to discharge, as often was the case with the high-threshold type F units, the monosynaptic reflex was facilitated by a 500-pps conditioning train applied proximal to a complete reversible cooling block of the PL nerve. In all 42 pairs studied, the weaker motor unit had the lower functional threshold for recruitment. Recruitment also invariably followed the order S greater than FR greater than FI greater than FF units. The motor unit of a pair with the higher resistance to fatigue thus always had the lower functional threshold. In 21 of the 22 pairs containing at least one type S motor unit, the unit with the slower-conducting motor axon had the lower functional threshold for recruitment.(ABSTRACT TRUNCATED AT 400 WORDS)

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