Convergence of Pattern Generator Outputs on a Common Mechanism of Diaphragm Motor Unit Recruitment

Abstract

Motor units are the final element of neuromotor control. In manner analogous to the organization of neuromotor control in other skeletal muscles, diaphragm motor units comprise phrenic motoneurons located in the cervical spinal cord that innervate the diaphragm muscle, the main inspiratory muscle in mammals. Diaphragm motor units play a primary role in sustaining ventilation, but are also active in other non-ventilatory behaviors, including coughing, sneezing, vomiting, defecation and parturition. Diaphragm muscle fibers comprise all fiber types. Thus, diaphragm motor units display substantial differences in contractile and fatigue properties, but importantly properties of the motoneuron and muscle fibers within a motor unit are matched. As in other skeletal muscles, diaphragm motor units are recruited in order such that motor units that display greater fatigue resistance are recruited earlier and more often than more fatigable motor units. The properties of the motor unit population are critical determinants of the function of a skeletal muscle across the range of possible motor tasks. Accordingly, fatigue-resistant motor units are sufficient to generate the forces necessary for ventilatory behaviors whereas more fatigable units are only activated during expulsive behaviors important for airway clearance. Neuromotor control of diaphragm motor units may reflect selective inputs from distinct pattern generators distributed according to the motor unit properties necessary to accomplish these different motor tasks. In contrast, widely-distributed inputs to phrenic motoneurons from various pattern generators (e.g., for breathing, coughing or vocalization) would dictate recruitment order based on intrinsic electrophysiological properties.

Impact of unilateral denervation on transdiaphragmatic pressure

“…Collectively, these afferent signals may modulate the central pattern generator for respiration (Feldman et al, 2013; Mantilla et al, 2014b). In this respect, these compensatory mechanisms remained intact after unilateral DNV since ventilation was maintained with an increase in central drive to contralateral phrenic motor neuron pool.…”

Semi-automated assessment of transdiaphragmatic pressure variability across motor behaviors

“…In recent studies, we showed that the period of phrenic motor unit recruitment spans the initial ~35–55% of the EMG peak duration across motor behaviors (Seven et al, 2013) and premotor drive to phrenic motor neurons is reflected by the rate of rise in DIAm EMG (Seven et al, 2014). Importantly, DIAm EMG measures such as the root mean squared EMG amplitude correlate with Pdi and both of these measures show a linear rate of rise during the period of motor unit recruitment (Mantilla et al, 2014; Mantilla et al, 2010). Accordingly, premotor drive (dPdi) was estimated for each inspiratory event by the change in Pdi amplitude within the initial ~30% of the inspiratory peak (i.e., 60 ms in mice).…”

“…The amplitude of a single breath, or inspiratory event, in turn relates to the specific premotor drive, and may be determined at the level of the motor unit pool for the different ventilatory muscles (Holstege, 2014; Mantilla et al, 2014). Analyses of variability in Pdi amplitude (i.e., variance and temporal structure of differences between successive inspiratory events) can provide useful insight into the neuromotor control of respiratory muscles, and may also inform conditions of injury, disease or aging.…”

“…Analyses of variability in Pdi amplitude (i.e., variance and temporal structure of differences between successive inspiratory events) can provide useful insight into the neuromotor control of respiratory muscles, and may also inform conditions of injury, disease or aging. Recent studies using data acquired via DIAm electromyography (EMG) provide important insight into the timing of motor unit recruitment and the level of premotor drive associated with DIAm activation across a range of ventilatory and higher force non-ventilatory behaviors (Gill et al, 2015; Mantilla et al, 2014; Seven et al, 2014; Seven et al, 2013). By developing a semi-automated method to analyze Pdi it is possible to obtain and evaluate large data sets containing information about the amplitude and premotor drive of successive inspiratory events across motor behaviors.…”

Localized Delivery of Brain-Derived Neurotrophic Factor-Expressing Mesenchymal Stem Cells Enhances Functional Recovery following Cervical Spinal Cord Injury

“…Phrenic motoneurons innervating the diaphragm muscle are located in cervical spinal cord segments C3-C6 in rats, [2][3][4] and receive predominantly ipsilateral descending excitatory bulbospinal inputs. 5,6 SH involves a unilateral transection of anterolateral funiculi at C2, which removes premotor drive to phrenic motoneurons, paralyzing the ipsilateral diaphragm muscle. [7][8][9][10][11][12][13][14] Following SH, there is gradual recovery of rhythmic diaphragm activity ipsilateral to injury, [15][16][17][18][19][20][21] suggesting neuroplasticity and strengthening of spared contralateral synaptic inputs to phrenic motoneurons.…”