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.

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 Recruitment of rat diaphragm motor units across motor behaviors with different levels of diaphragm activation

2014 ◽  
Vol 117 (11) ◽  
pp. 1308-1316 ◽  
Author(s):  
Yasin B. Seven ◽  
Carlos B. Mantilla ◽  
Gary C. Sieck
Keyword(s):  
Motor Unit ◽  
Motor Neurons ◽  
Motor Units ◽  
Motor Unit Recruitment ◽  
Diaphragm Muscle ◽  
Emg Activity ◽  
Motor Behaviors ◽  
Airway Occlusion ◽  
Recruitment Order ◽  
Central Drive

Phrenic motor neurons are recruited across a range of motor behaviors to generate varying levels of diaphragm muscle (DIAm) force. We hypothesized that DIAm motor units are recruited in a fixed order across a range of motor behaviors of varying force levels, consistent with the Henneman Size Principle. Single motor unit action potentials and compound DIAm EMG activities were recorded in anesthetized, neurally intact rats across different motor behaviors, i.e., eupnea, hypoxia-hypercapnia (10% O2 and 5% CO2), deep breaths, sustained airway occlusion, and sneezing. Central drive [estimated by root-mean-squared (RMS) EMG value 75 ms after the onset of EMG activity (RMS75)], recruitment delay, and onset discharge frequencies were similar during eupnea and hypoxia-hypercapnia. Compared with eupnea, central drive increased (∼25%) during deep breaths, and motor units were recruited ∼12 ms earlier ( P < 0.01). During airway occlusion, central drive was ∼3 times greater, motor units were recruited ∼30 ms earlier ( P < 0.01), and motor unit onset discharge frequencies were significantly higher ( P < 0.01). Recruitment order of motor unit pairs observed during eupnea was maintained for 98%, 87%, and 84% of the same pairs recorded during hypoxia-hypercapnia, deep breaths, and airway occlusion, respectively. Reversals in motor unit recruitment order were observed primarily if motor unit pairs were recruited <20 ms apart. These results are consistent with DIAm motor unit recruitment order being determined primarily by the intrinsic size-dependent electrophysiological properties of phrenic motor neurons.

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 Diaphragm muscle function following midcervical contusion injury in rats

2019 ◽  
Vol 126 (1) ◽  
pp. 221-230 ◽  
Author(s):  
Obaid U. Khurram ◽  
Matthew J. Fogarty ◽  
Sabhya Rana ◽  
Pangdra Vang ◽  
Gary C. Sieck ◽  
...  
Keyword(s):  
Motor Neuron ◽  
Motor Neurons ◽  
Force Generation ◽  
Diaphragm Muscle ◽  
Neuron Loss ◽  
Motor Behaviors ◽  
Contusion Injury ◽  
Motor Neuron Loss ◽  
The Impact ◽  
Over Time

Midcervical spinal cord contusion injury results in tissue damage, disruption of spinal pathways, and motor neuron loss. Unilateral C4 contusion results in loss of 40%–50% of phrenic motor neurons ipsilateral to the injury (~25% of the total phrenic motor neuron pool). Over time after unilateral C4 contusion injury, diaphragm muscle (DIAm) electromyogram activity increases both contralateral and ipsilateral to the side of injury in rats, suggesting compensation because of increased activation of the surviving motor neurons. However, the impact of contusion injury on DIAm force generation is less clear. Transdiaphragmatic pressure (Pdi) was measured across motor behaviors over time after unilateral C4 contusion injury in adult male Sprague-Dawley rats. Maximum Pdi (Pdimax) was elicited by bilateral phrenic nerve stimulation at 7 days postinjury. We hypothesized that Pdimax is reduced following unilateral C4 contusion injury, whereas ventilatory behaviors of the DIAm are unimpaired. In support of our hypothesis, Pdimax was reduced by ~25% after unilateral C4 contusion, consistent with the extent of phrenic motor neuron loss following contusion injury. One day after contusion injury, the Pdi amplitude during airway occlusion was reduced from ~30 to ~20 cmH2O, but this reduction was completely reversed by 7 days postinjury. Ventilatory behaviors (~10 cmH2O), DIAm-specific force, and muscle fiber cross-sectional area did not differ between the laminectomy and contusion groups. These results indicate that the large reserve capacity for DIAm force generation allows for higher-force motor behaviors to be accomplished despite motor neuron loss, likely reflecting changes in motor unit recruitment. NEW & NOTEWORTHY Respiratory muscles such as the diaphragm generate the pressures necessary to accomplish a variety of motor behaviors ranging from ventilation to near-maximal expulsive behaviors. However, the impact of contusion injury on diaphragm pressure generation across behaviors is not clear. The present study shows that contusion injury impairs maximal pressure generation while preserving the ability of the diaphragm to accomplish lower-force motor behaviors, likely reflecting changes in diaphragm motor unit recruitment.

scholarly journals Chronic assessment of diaphragm muscle EMG activity across motor behaviors

2011 ◽  
Vol 177 (2) ◽  
pp. 176-182 ◽  
Author(s):  
Carlos B. Mantilla ◽  
Yasin B. Seven ◽  
Juan N. Hurtado-Palomino ◽  
Wen-Zhi Zhan ◽  
Gary C. Sieck
Keyword(s):  
Diaphragm Muscle ◽  
Emg Activity ◽  
Motor Behaviors

scholarly journals Diaphragm muscle activity across respiratory motor behaviors in awake and lightly anesthetized rats

2018 ◽  
Vol 124 (4) ◽  
pp. 915-922 ◽  
Author(s):  
Federico Jimenez-Ruiz ◽  
Obaid U. Khurram ◽  
Wen-Zhi Zhan ◽  
Heather M. Gransee ◽  
Gary C. Sieck ◽  
...  
Keyword(s):  
Fixed Effects ◽  
Random Effect ◽  
Respiratory Muscles ◽  
Mixed Linear Model ◽  
Male Rats ◽  
Diaphragm Muscle ◽  
Emg Activity ◽  
Airway Patency ◽  
Motor Behaviors ◽  
Generating Capacity

Respiratory muscles such as the diaphragm are active across a range of behaviors including ventilation and higher-force behaviors necessary for maintenance of airway patency, and minimal information is available regarding anesthetic effects on the capacity of respiratory muscles to generate higher forces. The purpose of the present study was to determine whether diaphragm EMG activity during lower-force behaviors, such as eupnea and hypoxia-hypercapnia, is differentially affected compared with higher-force behaviors, such as a sigh, in lightly anesthetized animals. In adult male rats, chronically implanted diaphragm EMG electrodes were used to measure the effects of low-dose ketamine (30 mg/kg) and xylazine (3 mg/kg) on root mean square (RMS) EMG amplitude across a range of motor behaviors. A mixed linear model was used to evaluate the effects of ketamine-xylazine anesthesia on peak RMS EMG and ventilatory parameters, with condition (awake vs. anesthetized), behavior (eupnea, hypoxia-hypercapnia, sigh), side (left or right hemidiaphragm), and their interactions as fixed effects and animal as a random effect. Compared with the awake recordings, there was an overall reduction of peak diaphragm RMS EMG across behaviors during anesthesia, but this reduction was more pronounced during spontaneous sighs (which require ~60% of maximal diaphragm force). Respiratory rates and duty cycle during eupnea and hypoxia-hypercapnia were higher in awake compared with anesthetized conditions. These results highlight the importance of identifying anesthetic effects on a range of respiratory motor behaviors, including sighs necessary for maintaining airway patency. NEW & NOTEWORTHY Respiratory muscles accomplish a range of motor behaviors, with forces generated for ventilatory behaviors comprising only a small fraction of their maximal force generating capacity. Induction of anesthesia exerts more robust effects on the higher-force diaphragm motor behaviors such as sighs compared with eupnea. This novel information on effects of low, sedative doses of a commonly used anesthetic combination (ketamine-xylazine) highlights the importance of identifying anesthetic effects on a range of respiratory motor behaviors.

scholarly journals Inhibition of TrkB kinase activity impairs transdiaphragmatic pressure generation

2020 ◽  
Vol 128 (2) ◽  
pp. 338-344
Author(s):  
Miguel Pareja-Cajiao ◽  
Heather M. Gransee ◽  
Naomi A. Cole ◽  
Gary C. Sieck ◽  
Carlos B. Mantilla
Keyword(s):  
Neuromuscular Transmission ◽  
Kinase Activity ◽  
Motor Units ◽  
Diaphragm Muscle ◽  
Receptor Subtype ◽  
Transdiaphragmatic Pressure ◽  
Tracheal Occlusion ◽  
Motor Behaviors ◽  
Subtype B ◽  
Maximal Stimulation

Signaling via the tropomyosin-related kinase receptor subtype B (TrkB) regulates neuromuscular transmission, and inhibition of TrkB kinase activity by 1NMPP1 in TrkBF616A mice worsens neuromuscular transmission failure (NMTF). We hypothesized that acute inhibition of TrkB kinase activity will impair the ability of the diaphragm muscle to produce maximal transdiaphragmatic pressure (Pdi) without impacting the ability to generate forces associated with ventilation, consistent with the greater susceptibility to NMTF in motor units responsible for higher-force nonventilatory behaviors. Adult male and female TrkBF616A mice were injected with 1NMPP1 ( n = 8) or vehicle (DMSO; n = 8) 1 h before Pdi measurements during eupneic breathing, hypoxia/hypercapnia (10% O2/5% CO2), tracheal occlusion, spontaneous deep breaths (“sighs”) and during maximal activation elicited by bilateral phrenic nerve stimulation. In the vehicle-treated group, Pdi increased from ~10 cmH2O during eupnea and hypoxia/hypercapnia, to ~35 cmH2O during sighs and tracheal occlusion, and to ~65 cm H2O during maximal stimulation. There was no effect of acute 1NMPP1 treatment on Pdi generated during most behaviors, except during maximal stimulation (~30% reduction; P < 0.05). This reduction in maximal Pdi is generally similar to the worsening of NMTF previously reported with TrkB kinase inhibition in rodents. Accordingly, impaired TrkB signaling limits the range of motor behaviors accomplished by the diaphragm muscle and may contribute to neuromuscular dysfunction, primarily by impacting fatigable, higher force-generating motor units. NEW & NOTEWORTHY TrkB signaling plays an important role in maintaining neuromuscular function in the diaphragm muscle and may be necessary to accomplish the various motor behaviors ranging from ventilation to expulsive, behaviors requiring near-maximal forces. This study shows that inhibition of TrkB kinase activity impairs maximal pressure generation by the diaphragm muscle, but the ability to generate the lower pressures required for ventilatory behaviors is not impacted.

scholarly journals BDNF effects on functional recovery across motor behaviors after cervical spinal cord injury

2017 ◽  
Vol 117 (2) ◽  
pp. 537-544 ◽  
Author(s):  
Vivian Hernandez-Torres ◽  
Heather M. Gransee ◽  
Carlos B. Mantilla ◽  
Yao Wang ◽  
Wen-Zhi Zhan ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Motor Neurons ◽  
Neurotrophic Factor ◽  
Cervical Spinal Cord ◽  
Brain Derived Neurotrophic Factor ◽  
Diaphragm Muscle ◽  
Emg Activity ◽  
Motor Behaviors ◽  
Airway Occlusion ◽  
Spinal Cord Hemisection

Unilateral C2 cervical spinal cord hemisection (SH) disrupts descending excitatory drive to phrenic motor neurons, thereby paralyzing the ipsilateral diaphragm muscle (DIAm) during ventilatory behaviors. Recovery of rhythmic DIAm activity ipsilateral to injury occurs over time, consistent with neuroplasticity and strengthening of spared synaptic inputs to phrenic motor neurons. Localized intrathecal delivery of brain-derived neurotrophic factor (BDNF) to phrenic motor neurons after SH enhances recovery of eupneic DIAm activity. However, the impact of SH and BDNF treatment on the full range of DIAm motor behaviors has not been fully characterized. We hypothesized that all DIAm motor behaviors are affected by SH and that intrathecal BDNF enhances the recovery of both ventilatory and higher force, nonventilatory motor behaviors. An intrathecal catheter was placed in adult, male Sprague-Dawley rats at C4 to chronically infuse artificial cerebrospinal fluid (aCSF) or BDNF. DIAm electromyography (EMG) electrodes were implanted bilaterally to record activity across motor behaviors, i.e., eupnea, hypoxia-hypercapnia (10% O2 and 5% CO2), sighs, airway occlusion, and sneezing. After SH, ipsilateral DIAm EMG activity was evident in only 43% of aCSF-treated rats during eupnea, and activity was restored in all rats after BDNF treatment. The amplitude of DIAm EMG (root mean square, RMS) was reduced following SH during eupnea and hypoxia-hypercapnia in aCSF-treated rats, and BDNF treatment promoted recovery in both conditions. The amplitude of DIAm RMS EMG during sighs, airway occlusion, and sneezing was not affected by SH or BDNF treatment. We conclude that the effects of SH and BDNF treatment on DIAm activity depend on motor behavior. NEW & NOTEWORTHY This study demonstrates that after unilateral C2 spinal cord hemisection (SH), there are differences in the spontaneous recovery of diaphragm (DIAm) electromyographic activity during ventilatory compared with more forceful, nonventilatory motor behaviors. Furthermore, we show that intrathecal delivery of brain-derived neurotrophic factor (BDNF) at the level of the phrenic motor neuron pool enhances recovery of ipsilateral DIAm activity following SH, exerting main effects on recovery of ventilatory but not higher force, nonventilatory behaviors.

scholarly journals Effects of a Contusive Spinal Cord Injury on Spinal Motor Neuron Activity and Conduction Time in Rats

2020 ◽  
Author(s):  
Jordan A. Borrell ◽  
Dora Krizsan-Agbas ◽  
Randolph J. Nudo ◽  
Shawn B. Frost
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Spike Activity ◽  
Short Latency ◽  
Neuron Activity ◽  
Emg Activity ◽  
Conduction Time ◽  
Dorsal Midline ◽  
Cord Injury ◽  
Contusion Injury

AbstractObjectiveThe purpose of this study was to determine the effects of spinal cord injury (SCI) on spike activity evoked in the hindlimb spinal cord of the rat from cortical electrical stimulation.ApproachAdult, male, Sprague Dawley rats were randomly assigned to a Healthy or SCI group. SCI rats were given a 175 kDyn dorsal midline contusion injury at the level of the T8 vertebrae. At four weeks post-SCI, intracortical microstimulation (ICMS) was delivered at several sites in the hindlimb motor cortex of anesthetized rats, and evoked neural activity was recorded from corresponding sites throughout the dorsoventral depths of the spinal cord and EMG activity from hindlimb muscles.Main resultsIn healthy rats, post-ICMS spike histograms showed reliable, evoked spike activity during a short-latency epoch 10-12 ms after the initiation of the ICMS pulse train (short). Longer latency spikes occurred between ~20-60 ms, generally following a Gaussian distribution, rising above baseline at time LON, followed by a peak response (Lp), and then falling below baseline at time LOFF. EMG responses occurred between LON and Lp (25-27 ms). In SCI rats, short-latency responses were still present, long-latency responses were disrupted or eliminated, and EMG responses were never evoked. The retention of the short-latency responses indicates that spared descending spinal fibers, most likely via the cortico-reticulospinal pathway, can still depolarize spinal cord motor neurons after a dorsal midline contusion injury.SignificanceThis study provides novel insights into the role of alternate pathways for voluntary control of hindlimb movements after SCI that disrupts the corticospinal tract in the rat.

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