Breathing: Motor Control of Diaphragm Muscle

Fogarty, Matthew J.; Mantilla, Carlos B.; Sieck, Gary C.

doi:10.1152/physiol.00002.2018

Cited by 87 publications

(85 citation statements)

References 206 publications

(297 reference statements)

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“…Obviously, in old age, resilience of the force‐generating capacity of the DIAm to accomplish ventilatory behaviours ranging from eupnoea to airway occlusion without fatigue is essential to sustain life (Belman & Sieck, ; Fogarty & Sieck, ; Mantilla & Sieck, ; Sieck, ; Sieck & Fournier, ). Previously, we reported a model for DIAm motor unit recruitment to accomplish P di generation across a range of motor behaviours (Fogarty, Mantilla, & Sieck, ; Mantilla & Sieck, ; Sieck, ; Sieck & Fournier, ). In relationship to P di,max , the lower values of P di during eupnoea were achieved in both young and old rats by recruitment of only fatigue‐resistant DIAm motor units, comprising type I and type IIa fibres.…”

Section: Discussionmentioning

confidence: 99%

Impact of sarcopenia on diaphragm muscle fatigue

Fogarty

Mantilla

Sieck

2019

Experimental Physiology

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New Findings What is the central question of this study?Is the residual force generated by the diaphragm muscle after repeated activation reduced with sarcopenia, and is the residual force generated after fatiguing activation sufficient to sustain ventilatory behaviours of diaphragm muscle in young and old rats? What is the main finding and its importance?After diaphragm muscle fatigue, the residual specific force after 120 s of repeated stimulation was unaffected by ageing and was sufficient to accomplish ventilatory behaviours, but not expulsive manoeuvres (e.g. coughing). The inability to perform expulsive behaviours might underlie the increased susceptibility of older individuals to respiratory tract infections. Abstract Type IIx and/or IIb diaphragm muscle (DIAm) fibres make up more fatigable motor units that are more vulnerable to sarcopenia, i.e. age‐associated reductions of specific force and cross‐sectional area. In contrast, type I and IIa DIAm fibres form fatigue‐resistant motor units that are relatively unchanged with age. The fatigue resistance of the DIAm is assessed by normalizing the residual force generated after a period of repeated supramaximal stimulation (e.g. 120 s) to the initial maximal force. Given that sarcopenia primarily affects more fatigable DIAm motor units, apparent fatigue resistance improves with ageing. However, the central question is whether there is an ageing‐related difference in the residual force generated by the DIAm after repeated stimulation and whether this force is sufficient to sustain ventilatory behaviours of DIAm. In 6‐ and 24‐month‐old Fischer 344 rats, we assessed the loss of ex vivo DIAm force throughout 120 s of repeated supramaximal stimulation at 10, 40 and 75 Hz. We found that relative fatigue resistance improved in older rats at 40 and 75 Hz stimulation. Across all stimulation frequencies, DIAm residual force was unchanged with age (∼5 N cm−2). We conclude that ageing increases the relative contribution of type I and IIa fibres to DIAm force, with decreased contributions of type IIx and/or IIb fibres. The residual force generated by the DIAm after repeated stimulation is sufficient to accomplish ventilatory behaviours, regardless of age.

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Section: Discussionmentioning

confidence: 99%

Impact of sarcopenia on diaphragm muscle fatigue

Fogarty

Mantilla

Sieck

2019

Experimental Physiology

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“…However, for a given motor unit type, MN characteristics are less variable. Thus, MNs of type S and FR units are smaller (low capacitance), more easily excitable, have a lower innervation ratio, and smaller axon diameters, while MNs of type FInt and FF motor units are larger (high capacitance), less easily excitable, have a lower innervation ratio and smaller axon diameters (Schiaffino and Reggiani, ; Fogarty et al, ; Manuel et al, ). Importantly, the dendritic length and membrane surface area is larger in F compared to S type motor units (Cullheim et al, ; Leroy et al, ).…”

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confidence: 99%

“…Mouse models based on known genetic causes of ALS, particularly SOD1 mutations (Rosen et al, ), have successfully modeled loss of MNs (Gurney et al, ; Ngo et al, ; Steyn et al, ). Losses of MNs appear to be size‐dependent, with the larger FInt and FF MNs vulnerable (Hegedus et al, ; Hegedus et al, ; Kaplan et al, ; Dukkipati et al, ; Fogarty ). In multiple neuronal populations within ALS mouse models, dendritic degeneration is observed before neuronal death occurs (Ma and Vacca‐Galloway, ; Spalloni et al, ; Amendola and Durand, ; Sgobio et al, ; Nieto‐Gonzalez et al, ; Filipchuk and Durand, ; Huang et al, ; Jara et al, ; Fogarty et al, ; Jara et al, ; Saba et al, ; Wu et al, ; Fogarty et al, ; Fogarty et al, ; Handley et al, ; Fogarty et al, ).…”

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confidence: 99%

Size‐Dependent Vulnerability of Lumbar Motor Neuron Dendritic Degeneration in SOD1^G93A Mice

Fogarty

Lavidis

et al. 2019

The Anatomical Record

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The motor neuron (MN) soma surface area is correlated with motor unit type. Larger MNs innervate fast fatigue-intermediate (FInt) or fast-fatiguable (FF) muscle fibers in type FInt and FF motor units, respectively. Smaller MNs innervate slow-twitch fatigue-resistant (S) or fast fatigue-resistant (FR) muscle fibers in type S and FR motor units, respectively. In amyotrophic lateral sclerosis (ALS), FInt and FF motor units are more vulnerable, with denervation and MN death occurring for these units before the more resilient S and FR units. Abnormal MN dendritic arbors have been observed in ALS in humans and rodent models. We used a Golgi-Cox impregnation protocol to examine soma size-dependent changes in the dendritic morphology of lumbar MNs in SOD1 G93A mice, a model of ALS, at pre-symptomatic, onset and mid-disease stages. In wildtype control mice, the relationship between MN soma surface area and dendritic length or dendritic spine number was highly linear (i.e., increased MN soma size correlated with increased dendritic length and spines). By contrast, in SOD1 G93A mice, this linear relationship was lost and dendritic length reduction and spine loss were observed in larger MNs, from pre-symptomatic stages onward. These changes correlated with the neuromotor symptoms of ALS in rodent models. At presymptomatic ages, changes were restricted to the larger MNs, likely to comprise vulnerable FInt and FF motor units. Our results suggest morphological changes of MN dendrites and dendritic spines are likely to contribute ALS pathogenesis, not compensate for it. Anat

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“…Previous work in other animal models have identified multifunctional muscles involved in more than one motor behavior: swimming and crawling in C. elegans (Pierce-Shimomura et al 2008; Vidal-Gadea et al 2011; Butler et al 2015) and leech (Briggman and Kristan 2006); walking and flight in locust (Ramirez and Pearson 1988); respiratory and non-respiratory functions of mammalian diaphragm muscle (Lieske et al 2000; Fogarty et al 2018) unifunctional muscles which are only active in one specific behavior in the lobster Homarus americanus (Mulloney et al 2014); swimming in the marine mollusk Tritonia diomedea (Popescu and Frost 2002); and muscles in different regions of crab and lobster stomach (Bucher et al 2006; Briggman and Kristan 2008). Our single-muscle calcium imaging data indicates that all imaged larval body wall muscles are bifunctional and are activated during both forward and backward locomotion.…”

Section: Discussionmentioning

confidence: 99%

ADrosophilalarval premotor/motor neuron connectome generating two behaviors via distinct spatio-temporal muscle activity

Zarin

Mark

Cardona

et al. 2019

Preprint

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Animals generate diverse motor behaviors, yet how the same motor neurons generate distinct behaviors remains an open question.Drosophilalarvae have multiple behaviors – e.g. forward crawling, backward crawling, self-righting and escape – and all of the body wall motor neurons (MNs) driving these behaviors have been identified. Despite impressive progress in mapping larval motor circuits, the role of most motor neurons in locomotion remains untested, the majority of premotor neurons (PMNs) remain to be identified, and a full understanding of proprioceptor-PMN-MN connectivity is missing. Here we report a comprehensive larval proprioceptor-PMN-MN connectome; describe individual muscle/MN phase activity during both forward and backward locomotor behaviors; identify PMN-MN connectivity motifs that could generate muscle activity phase relationships, plus selected experimental validation; identify proprioceptor-PMN connectivity that provides an anatomical explanation for the role of proprioception in promoting locomotor velocity; and identify a new candidate escape motor circuit. Finally, we generate a recurrent network model that produces the observed sequence of motor activity, showing that the identified pool of premotor neurons is sufficient to generate two distinct larval behaviors. We conclude that different locomotor behaviors can be generated by a specific group of premotor neurons generating behavior-specific motor rhythms.

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Breathing: Motor Control of Diaphragm Muscle

Cited by 87 publications

References 206 publications

Impact of sarcopenia on diaphragm muscle fatigue

Impact of sarcopenia on diaphragm muscle fatigue

Size‐Dependent Vulnerability of Lumbar Motor Neuron Dendritic Degeneration in SOD1^G93A Mice

ADrosophilalarval premotor/motor neuron connectome generating two behaviors via distinct spatio-temporal muscle activity

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Breathing: Motor Control of Diaphragm Muscle

Cited by 87 publications

References 206 publications

Impact of sarcopenia on diaphragm muscle fatigue

Impact of sarcopenia on diaphragm muscle fatigue

Size‐Dependent Vulnerability of Lumbar Motor Neuron Dendritic Degeneration in SOD1G93A Mice

ADrosophilalarval premotor/motor neuron connectome generating two behaviors via distinct spatio-temporal muscle activity

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Product

Resources

About

Size‐Dependent Vulnerability of Lumbar Motor Neuron Dendritic Degeneration in SOD1^G93A Mice