Invited Review: Mechanisms underlying motor unit plasticity in the respiratory system

2003 ◽  
Vol 94 (3) ◽  
pp. 1230-1241 ◽  
Author(s):  
Carlos B. Mantilla ◽  
Gary C. Sieck
Keyword(s):  
Motor Unit ◽  
Skeletal Muscles ◽  
Neuromuscular Junctions ◽  
Muscle Fibers ◽  
Respiratory Muscles ◽  
Motor Units ◽  
Diaphragm Muscle ◽  
Neuromotor Control ◽  
Phrenic Motoneurons

Neuromotor control of skeletal muscles, including respiratory muscles, is ultimately dependent on the function of the motor unit (comprising an individual motoneuron and the muscle fibers it innervates). Considerable diversity exists across diaphragm motor units, yet remarkable homogeneity is present (and maintained) within motor units. In recent years, the mechanisms underlying the development and adaptability of respiratory motor units have received great attention, leading to significant advances in our understanding of diaphragm motor unit plasticity. For example, following imposed inactivity of the diaphragm muscle, there are changes at phrenic motoneurons, neuromuscular junctions, and muscle fibers that tend to restore the ability of the diaphragm to sustain ventilation. The role of activity, neurotrophins, and other growth factors in modulating this adaptability is discussed.

scholarly journals Breathing: Motor Control of Diaphragm Muscle

Physiology ◽  
2018 ◽  
Vol 33 (2) ◽  
pp. 113-126 ◽  
Author(s):  
Matthew J. Fogarty ◽  
Carlos B. Mantilla ◽  
Gary C. Sieck
Keyword(s):  
Neural Network ◽  
Motor Control ◽  
Motor Unit ◽  
Motor Neurons ◽  
Muscle Fibers ◽  
Motor Units ◽  
Diaphragm Muscle ◽  
Final Output ◽  
Unit Organization

Breathing occurs without thought but is controlled by a complex neural network with a final output of phrenic motor neurons activating diaphragm muscle fibers (i.e., motor units). This review considers diaphragm motor unit organization and how they are controlled during breathing as well as during expulsive behaviors.

scholarly journals Key aspects of phrenic motoneuron and diaphragm muscle development during the perinatal period

2008 ◽  
Vol 104 (6) ◽  
pp. 1818-1827 ◽  
Author(s):  
Carlos B. Mantilla ◽  
Gary C. Sieck
Keyword(s):  
Muscle Development ◽  
Respiratory Muscles ◽  
Motor Units ◽  
Perinatal Period ◽  
Diaphragm Muscle ◽  
Postnatal Maturation ◽  
Motor Behaviors ◽  
Phrenic Motoneurons ◽  
Phrenic Motoneuron ◽  
Key Aspects

At the time of birth, respiratory muscles must be activated to sustain ventilation. The perinatal development of respiratory motor units (comprising an individual motoneuron and the muscle fibers it innervates) shows remarkable features that enable mammals to transition from in utero conditions to the air environment in which the remainder of their life will occur. In addition, significant postnatal maturation is necessary to provide for the range of motor behaviors necessary during breathing, swallowing, and speech. As the main inspiratory muscle, the diaphragm muscle (and the phrenic motoneurons that innervate it) plays a key role in accomplishing these behaviors. Considerable diversity exists across diaphragm motor units, but the determinant factors for this diversity are unknown. In recent years, the mechanisms underlying the development of respiratory motor units have received great attention, and this knowledge may provide the opportunity to design appropriate interventions for the treatment of respiratory disease not only in the perinatal period but likely also in the adult.

scholarly journals Diaphragm electromyographic activity following unilateral midcervical contusion injury in rats

2017 ◽  
Vol 117 (2) ◽  
pp. 545-555 ◽  
Author(s):  
Sabhya Rana ◽  
Gary C. Sieck ◽  
Carlos B. Mantilla
Keyword(s):  
Motor Units ◽  
Diaphragm Muscle ◽  
Emg Activity ◽  
High Threshold ◽  
Perineuronal Net ◽  
Neural Drive ◽  
Motor Behaviors ◽  
Neuromotor Control ◽  
Phrenic Motoneurons ◽  
Contusion Injury

Contusion-type injuries to the spinal cord are characterized by tissue loss and disruption of spinal pathways. Midcervical spinal cord injuries impair the function of respiratory muscles and may contribute to significant respiratory complications. This study systematically assessed the impact of a 100-kDy unilateral C4 contusion injury on diaphragm muscle activity across a range of motor behaviors in rats. Chronic diaphragm electromyography (EMG) was recorded before injury and at 1 and 7 days postinjury (DPI). Histological analyses assessed the extent of perineuronal net formation, white-matter sparing, and phrenic motoneuron loss. At 7 DPI, ∼45% of phrenic motoneurons were lost ipsilaterally. Relative diaphragm root mean square (RMS) EMG activity increased bilaterally across a range of motor behaviors by 7 DPI. The increase in diaphragm RMS EMG activity was associated with an increase in neural drive (RMS value at 75 ms after the onset of diaphragm activity) and was more pronounced during higher force, nonventilatory motor behaviors. Animals in the contusion group displayed a transient decrease in respiratory rate and an increase in burst duration at 1 DPI. By 7 days, following midcervical contusion, there was significant perineuronal net formation and white-matter loss that spanned 1 mm around the injury epicenter. Taken together, these findings are consistent with increased recruitment of remaining motor units, including more fatigable, high-threshold motor units, during higher force, nonventilatory behaviors. Changes in diaphragm EMG activity following midcervical contusion injury reflect complex adaptations in neuromotor control that may increase the risk of motor-unit fatigue and compromise the ability to sustain higher force diaphragm efforts. NEW & NOTEWORTHY The present study shows that unilateral contusion injury at C4 results in substantial loss of phrenic motoneurons but increased diaphragm muscle activity across a range of ventilatory and higher force, nonventilatory behaviors. Measures of neural drive indicate increased descending input to phrenic motoneurons that was more pronounced during higher force, nonventilatory behaviors. These findings reveal novel, complex adaptations in neuromotor control following injury, suggestive of increased recruitment of more fatigable, high-threshold motor units.

Morphological Adaptations of Neuromuscular Junctions Depend on Fiber Type

1997 ◽  
Vol 22 (3) ◽  
pp. 197-230 ◽  
Author(s):  
Gary C. Sieck ◽  
Y. S. Prakash
Keyword(s):  
Neuromuscular Junctions ◽  
Fiber Type ◽  
Muscle Fibers ◽  
Motor Units ◽  
Diaphragm Muscle ◽  
Dimensional Structure ◽  
Type I ◽  
Fiber Types ◽  
Structural And Functional Properties ◽  
Fast Twitch

The neuromuscular junction (NMJ) forms the communicative types of motor units, which are recruited selectively to accomplish various link between motoneurons and muscle fibers. The properties of motoneurons and muscle fibers are matched in different motor behaviors. Motor units and muscle fibers can be classified based upon structural and functional properties, reflecting the essential match between motoneuron and muscle fiber. Using a three-color immunofluorescence technique combined with confocal microscopy, we examined the three-dimensional structure of pre- and postsynaptic elements of NMJs on different fiber types in the rat diaphragm muscle. On type I and IIa fibers, comprising slow-twitch and fast-twitch fatigue-resistant motor units, the structure of NMJs is far less complex than on type IIx and IIb fibers comprising fast-twitch fatigue-intermediate and fast-twitch fatigable motor units. We also found a greater extent of overlap between pre- and postsynaptic elements of NMJs on type I and IIa fibers. This review focuses on these normal phenotypic differences in NMJ properties and on the adaptations that occur under various conditions of altered use. Key words: nerve terminal, motor endplate, morphology, neuromuscular transmission, fatigue, plasticity

Summation of motor unit tensions in the tibialis posterior muscle of the cat under isometric and nonisometric conditions

1991 ◽  
Vol 66 (6) ◽  
pp. 1838-1846 ◽  
Author(s):  
R. K. Powers ◽  
M. D. Binder
Keyword(s):  
Motor Unit ◽  
Muscle Fibers ◽  
Stimulus Frequency ◽  
Muscle Length ◽  
Motor Units ◽  
Force Transducer ◽  
Tibialis Posterior ◽  
Single Motor Units ◽  
Individual Motor ◽  
Stimulation Of

1. The tension produced by the combined stimulation of two to four single motor units of the cat tibialis posterior muscle was compared with the algebraic sum of the tensions produced by each individual motor unit. Comparisons were made under isometric conditions and during imposed changes in muscle length. 2. Under isometric conditions, the tension resulting from combined stimulation of units displayed marked nonlinear summation, as previously reported in other cat hindlimb muscles. On average, the measured tension was approximately 20% greater than the algebraic sum of the individual unit tensions. However, small trapezoidal movements imposed on the muscle during stimulation significantly reduced the degree of nonlinear summation both during and after the movement. This effect was seen with imposed movements as small as 50 microns. 3. The degree of nonlinear summation was not dependent on motor unit size or on stimulus frequency. The effect was also unrelated to tendon compliance because the degree of nonlinear summation of motor unit forces was unaffected by the inclusion of different amounts of the external tendon between the muscle and the force transducer. 4. Our results support previous suggestions that the force measured when individual motor units are stimulated under isometric conditions is reduced by friction between the active muscle fibers and adjacent passive fibers. These frictional effects are likely to originate in the connective tissue matrix connecting adjacent muscle fibers. However, because these effects are virtually eliminated by small movements, linear summation of motor unit tensions should occur at low force levels under nonisometric conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals The microRNA, miR-133b, functions to slow Duchenne muscular dystrophy pathogenesis

2020 ◽  
Author(s):  
Thomas Taetzsch ◽  
Dillon Shapiro ◽  
Randa Eldosougi ◽  
Tracey Myers ◽  
Robert Settlage ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Skeletal Muscles ◽  
Tibialis Anterior Muscle ◽  
Muscle Fibers ◽  
Progressive Degeneration ◽  
Protein Encoding ◽  
Small Muscle ◽  
Encoding Genes

AbstractDuchenne muscular dystrophy (DMD) is characterized by progressive degeneration of skeletal muscles. To date, there are no treatments available to slow or prevent the disease. Hence, it remains essential to identify molecular factors that promote muscle biogenesis since they could serve as therapeutic targets for treating DMD. While the muscle enriched microRNA, miR-133b, has been implicated in the biogenesis of muscle fibers, its role in DMD remains unknown. To assess the role of miR-133b in DMD-affected skeletal muscles, we genetically ablated miR-133b in the mdx mouse model of DMD. In the absence of miR-133b, the tibialis anterior muscle of juvenile and adult mdx mice is populated by small muscle fibers with centralized nuclei, exhibits increased fibrosis, and thickened interstitial space. Additional analysis revealed that loss of miR-133b exacerbates DMD-pathogenesis partly by altering the number of satellite cells and levels of protein-encoding genes, including previously identified miR-133b targets as well as genes involved in cell proliferation and fibrosis. Altogether, our data demonstrate that skeletal muscles utilize miR-133b to mitigate the deleterious effects of DMD.

Maximal force as a function of anatomical features of motor units in the cat tibialis anterior

1987 ◽  
Vol 57 (6) ◽  
pp. 1730-1745 ◽  
Author(s):  
S. C. Bodine ◽  
R. R. Roy ◽  
E. Eldred ◽  
V. R. Edgerton
Keyword(s):  
Motor Unit ◽  
Tibialis Anterior ◽  
Periodic Acid ◽  
Muscle Fibers ◽  
Motor Units ◽  
Cross Sectional Area ◽  
Sectional Area ◽  
Periodic Acid Schiff ◽  
Cross Sectional ◽  
Single Motor Unit

In 11 tibialis anterior muscles of the cat, a single motor unit was characterized physiologically and subsequently depleted of its glycogen through repetitive stimulation of an isolated ventral root filament. Muscle cross sections were stained for glycogen using a periodic acid-Schiff reaction, and single-fiber optical densities were determined to identify those fibers belonging to the stimulated motor unit. Innervation ratios were determined by counting the total number of muscle fibers in a motor unit in sections taken through several levels of the muscle. The average innervation ratios for the fast, fatigueable (FF) and fast, fatigue-resistant (FR) units were similar. However, the slow units (S) contained 61% fewer fibers than the fast units (FF and FR). Muscle fibers belonging to S and FR units were similar in cross-sectional area, whereas fibers belonging to FF units were significantly larger than fibers belonging to either S or FR units. Additionally, muscle fibers innervated by a single motoneuron varied by two- to eightfold in cross-sectional area. Specific tensions, based on total cross-sectional area determined by summing the areas of all muscle fibers of each unit, showed a modest difference between fast and slow units, the means being 23.5 and 17.2 N X cm-2, respectively. Variations in maximum tension among units could be explained principally by innervation ratio, although fiber cross-sectional area and specific tension did contribute to differences between unit types.

Further evidence of incomplete neural control of muscle properties in cat tibialis anterior motor units

1995 ◽  
Vol 268 (2) ◽  
pp. C527-C534 ◽  
Author(s):  
G. A. Unguez ◽  
R. R. Roy ◽  
D. J. Pierotti ◽  
S. Bodine-Fowler ◽  
V. R. Edgerton
Keyword(s):  
Motor Unit ◽  
Tibialis Anterior ◽  
Neural Control ◽  
Periodic Acid ◽  
Muscle Fibers ◽  
Motor Units ◽  
Fiber Types ◽  
Muscle Properties ◽  
Periodic Acid Schiff ◽  
The Mean

To examine the influence of a motoneuron in maintaining the phenotype of the muscle fibers it innervates, myosin heavy chain (MHC) expression, succinate dehydrogenase (SDH) activity, and cross-sectional area (CSA) of a sample of fibers belonging to a motor unit were studied in the cat tibialis anterior 6 mo after the nerve branches innervating the anterior compartment were cut and sutured near the point of entry into the muscle. The mean, range, and coefficient of variation for the SDH activity and the CSA for both motor unit and non-motor unit fibers for each MHC profile and from each control and each self-reinnervated muscle studied was obtained. Eight motor units were isolated from self-reinnervated muscles using standard ventral root filament testing techniques, tested physiologically, and compared with four motor units from control muscles. Motor units from self-reinnervated muscles could be classified into the same physiological types as those found in control tibialis anterior muscles. The muscle fibers belonging to a unit were depleted of glycogen via repetitive stimulation and identified in periodic acid-Schiff-stained frozen sections. Whereas muscle fibers in control units expressed similar MHCs, each motor unit from self-reinnervated muscles contained a mixture of fiber types. In each motor unit, however, there was a predominance of fibers with the same MHC profile. The relative differences in the mean SDH activities found among fibers of different MHC profiles within a unit after self-reinnervation and those found among fibers in control muscles were similar, i.e., fast-2 < fast-1 < or = slow MHC fibers.(ABSTRACT TRUNCATED AT 250 WORDS)

Properties of self-reinnervated motor units of medial gastrocnemius of cat. II. Axotomized motoneurons and time course of recovery

1986 ◽  
Vol 55 (5) ◽  
pp. 947-965 ◽  
Author(s):  
R. C. Foehring ◽  
G. W. Sypert ◽  
J. B. Munson
Keyword(s):  
Electrical Properties ◽  
Motor Unit ◽  
Fatigue Resistance ◽  
Time Course ◽  
Muscle Fibers ◽  
Motor Units ◽  
Input Resistance ◽  
Medial Gastrocnemius ◽  
Muscle Properties ◽  
Fast Twitch

This study tested the hypothesis that functional connection to muscle is necessary for expression of normal motoneuron electrical properties. Also examined was the time course of self-reinnervation. Properties of individual medial gastrocnemius (MG) motor units were examined following section and reanastomosis of the MG nerve. Stages examined were 3-5 wk (prior to reinnervation, no-re), 5-6 wk (low-re), 9-10 wk (med-re), and 9 mo (long-re, preceding paper) after nerve section. Motor units were classified on the basis of their mechanical response as type fast twitch, fast fatiguing (FF), fast twitch with intermediate fatigue resistance (FI), fast twitch, fatigue resistant (FR), or slow twitch, fatigue resistant (S) (11, 24). Motoneuron electrical properties were measured. Muscle fibers were classified using histochemical methods as type fast glycolytic (FG), fast oxidative glycolytic (FOG), or slow oxidative (SO) (60). Prior to functional reinnervation, MG motoneurons exhibited increased input resistance, decreased rheobase, decreased rheobase/input resistance, and decreased axonal conduction velocity. There was no change in mean afterhyperpolarization (AHP) half-decay time. Normal relationships between motoneuron electrical properties were lost. These data are consistent with dedifferentiation of motoneuron properties following axotomy (35, 47). At 5-6 wk after reanastomosis, motor-unit tensions were small, and motoneuron membrane electrical properties were unchanged from the no-re stage. There were no differences in motoneuron electrical properties between cells that elicited muscle contraction and those that did not. Motor-unit types were first recognizable at the med-re stage. The proportions of fast and slow motor units were similar to normal MG. Within the fast units, there were fewer type-FF units and more type-FI and type-FR units than normal, reflecting a general increase in fatigue resistance at this stage. Neither motoneuron membrane electrical properties nor muscle contractile properties had reached normal values, although both were changed in that direction from the low-re stage. Normal relationships between muscle properties, between motoneuron properties, and between motoneuron and muscle properties were re-established. The correspondence between motor-unit type and motoneuron type was similar to normal or 9 mo reinnervated MG. Muscle-unit tetanic tensions became larger with time after reinnervation. Most of the increase in muscle tension beyond the med-re stage could be accounted for by increase in muscle fiber area. There was an increased proportion of SO muscle fibers observed in the med-re muscles, as at the long-re stage.(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals Basal lamina directs acetylcholinesterase accumulation at synaptic sites in regenerating muscle.

1985 ◽  
Vol 101 (3) ◽  
pp. 735-743 ◽  
Author(s):  
L Anglister ◽  
U J McMahan
Keyword(s):  
Plasma Membrane ◽  
Neuromuscular Junction ◽  
Basal Lamina ◽  
Acetylcholine Receptors ◽  
Skeletal Muscles ◽  
Ache Activity ◽  
Neuromuscular Junctions ◽  
Muscle Fibers ◽  
Synaptic Cleft

In skeletal muscles that have been damaged in ways which spare the basal lamina sheaths of the muscle fibers, new myofibers develop within the sheaths and neuromuscular junctions form at the original synaptic sites on them. At the regenerated neuromuscular junctions, as at the original ones, the muscle fibers are characterized by junctional folds and accumulations of acetylcholine receptors and acetylcholinesterase (AChE). The formation of junctional folds and the accumulation of acetylcholine receptors is known to be directed by components of the synaptic portion of the myofiber basal lamina. The aim of this study was to determine whether or not the synaptic basal lamina contains molecules that direct the accumulation of AChE. We crushed frog muscles in a way that caused disintegration and phagocytosis of all cells at the neuromuscular junction, and at the same time, we irreversibly blocked AChE activity. New muscle fibers were allowed to regenerate within the basal lamina sheaths of the original muscle fibers but reinnervation of the muscles was deliberately prevented. We then stained for AChE activity and searched the surface of the new muscle fibers for deposits of enzyme they had produced. Despite the absence of innervation, AChE preferentially accumulated at points where the plasma membrane of the new muscle fibers was apposed to the regions of the basal lamina that had occupied the synaptic cleft at the neuromuscular junctions. We therefore conclude that molecules stably attached to the synaptic portion of myofiber basal lamina direct the accumulation of AChE at the original synaptic sites in regenerating muscle. Additional studies revealed that the AChE was solubilized by collagenase and that it remained adherent to basal lamina sheaths after degeneration of the new myofibers, indicating that it had become incorporated into the basal lamina, as at normal neuromuscular junctions.

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