Long-term facilitation of ipsilateral but not contralateral phrenic output after cervical spinal cord hemisection

Doperalski, Nicholas J.; Fuller, David D.

doi:10.1016/j.expneurol.2006.01.035

Cited by 47 publications

(42 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The relative decrease in MAP during hypoxia was similar in PhrX-LTF and PhrI-LTF rats: Ϫ20 Ϯ 3 and Ϫ28 Ϯ 6% baseline, respectively (P ϭ 0.25). Similar to prior phrenic LTF studies (8,14,41), MAP also tended to decrease slightly over the course of the experimental protocol; however, statistical significance was reached in only PhrI-LTF rats (P ϭ 0.035; Table 1). …”

Section: Discussionmentioning

confidence: 56%

“…Since even small increases in Pa CO 2 will increase the overall output of phrenic motoneurons (32,65), elevated Pa CO 2 may impair or reduce subsequent LTF expression via a "ceiling effect." In other words, if phrenic motor output is relatively high during baseline (pre-IH) conditions, capacity for increased motoneuron recruitment or rate coding during the posthypoxic period may be reduced (14). Consistent with this idea, phrenic LTF is difficult to evoke in phrenic neurograms recorded contralateral to cervical spinal cord hemisection injury (14), a condition that results in robust compensatory increases in contralateral phrenic output (51).…”

Section: Implications For the Study Of Respiratory Ltfmentioning

confidence: 53%

“…In other words, if phrenic motor output is relatively high during baseline (pre-IH) conditions, capacity for increased motoneuron recruitment or rate coding during the posthypoxic period may be reduced (14). Consistent with this idea, phrenic LTF is difficult to evoke in phrenic neurograms recorded contralateral to cervical spinal cord hemisection injury (14), a condition that results in robust compensatory increases in contralateral phrenic output (51). In contrast, Lee and colleagues (35) recently demonstrated that raising PET CO 2 by ϳ4 Torr above eupneic values is a prerequisite for induction of ventilatory LTF (including increased frequency and tidal volume) in spontaneously breathing humans.…”

Section: Implications For the Study Of Respiratory Ltfmentioning

confidence: 99%

“…The general procedures have been described recently (14,36). Rats were anesthetized with isoflurane (5% in 100% O 2) in a closed chamber and then transferred to a nose cone (2-3% isoflurane in 50% O 2-balance N2).…”

Section: Experimental Preparationmentioning

confidence: 99%

See 3 more Smart Citations

Phrenicotomy alters phrenic long-term facilitation following intermittent hypoxia in anesthetized rats

Sandhu

Lee

Fregosi

et al. 2010

Journal of Applied Physiology

View full text Add to dashboard Cite

Sandhu MS, Lee KZ, Fregosi RF, Fuller DD. Phrenicotomy alters phrenic long-term facilitation following intermittent hypoxia in anesthetized rats. J Appl Physiol 109: 279 -287, 2010. First published April 15, 2010 doi:10.1152/japplphysiol.01422.2009 can induce a persistent increase in neural drive to the respiratory muscles known as long-term facilitation (LTF). LTF of phrenic inspiratory activity is often studied in anesthetized animals after phrenicotomy (PhrX), with subsequent recordings being made from the proximal stump of the phrenic nerve. However, severing afferent and efferent axons in the phrenic nerve has the potential to alter the excitability of phrenic motoneurons, which has been hypothesized to be an important determinant of phrenic LTF. Here we test the hypothesis that acute PhrX influences immediate and long-term phrenic motor responses to hypoxia. Phrenic neurograms were recorded in anesthetized, ventilated, and vagotomized adult male rats with intact phrenic nerves or bilateral PhrX. Data were obtained before (i.e., baseline), during, and after three 5-min bouts of isocapnic hypoxia. Inspiratory burst amplitude during hypoxia (%baseline) was greater in PhrX than in phrenic nerve-intact rats (P Ͻ 0.001). Similarly, burst amplitude 55 min after IH was greater in PhrX than in phrenic nerve-intact rats (175 Ϯ 9 vs. 126 Ϯ 8% baseline, P Ͻ 0.001).In separate experiments, phrenic bursting was recorded before and after PhrX in the same animal. Afferent bursting that was clearly observable in phase with lung deflation was immediately abolished by PhrX. The PhrX procedure also induced a form of facilitation as inspiratory burst amplitude was increased at 30 min post-PhrX (P ϭ 0.01 vs. pre-PhrX). We conclude that, after PhrX, axotomy of phrenic motoneurons and, possibly, removal of phrenic afferents result in increased phrenic motoneuron excitability and enhanced LTF following IH. axotomy; phrenic motoneurons; plasticity EXPOSURE TO INTERMITTENT HYPOXIA (IH) over short periods (e.g., minutes to hours) can evoke a persistent increase in respiratory motor output, termed long-term facilitation (LTF) (35,48,50). LTF has been observed in awake (26, 35) and sleeping humans (53) and in a wide range of animal species (22,46,48). The mechanisms underlying LTF have been studied extensively over the last 10 -15 years, primarily in anesthetized animals (reviewed in Refs. 42,49,50). In anesthetized animals, LTF is typically manifest as an increase in the inspiratory burst amplitude of phrenic (19) and/or hypoglossal (XII) extracellular nerve recordings (20). Recordings of in vivo (19) and in vitro (10) respiratory motor LTF are typically made from cut respiratory muscle nerves. More specifically, the phrenic and/or XII nerves are cut, and subsequent extracellular recordings are made from the central end of the nerve. This procedure can provide stability to the neurophysiological recording procedures, particularly when a dorsal surgical approach is used, but also has the potential to alter respiratory motor output and...

show abstract

Section: Discussionmentioning

confidence: 56%

Section: Implications For the Study Of Respiratory Ltfmentioning

confidence: 53%

Section: Implications For the Study Of Respiratory Ltfmentioning

confidence: 99%

Section: Experimental Preparationmentioning

confidence: 99%

See 2 more Smart Citations

Phrenicotomy alters phrenic long-term facilitation following intermittent hypoxia in anesthetized rats

Sandhu

Lee

Fregosi

et al. 2010

Journal of Applied Physiology

View full text Add to dashboard Cite

show abstract

“…following C2HS. Indeed, even when both phrenic nerves are intact, C2HS injury causes a robust enhancement of contralateral phrenic output (8,15,36,39).We reasoned, therefore, that measuring inspiratory V T immediately before and after an acute ipsilateral phrenicotomy procedure could enable a more definitive assessment of the functional significance of the sCPP. In other words, the immediate (i.e., "next breath") drop in V T resulting from disruption of the sCPP should provide a quantitative estimate of its importance.…”

mentioning

confidence: 99%

Contribution of the spontaneous crossed-phrenic phenomenon to inspiratory tidal volume in spontaneously breathing rats

Dougherty

Lee

Lane

et al. 2012

Journal of Applied Physiology

View full text Add to dashboard Cite

Dougherty BJ, Lee KZ, Lane MA, Reier PJ, Fuller DD. Contribution of the spontaneous crossed-phrenic phenomenon to inspiratory tidal volume in spontaneously breathing rats. J Appl Physiol 112: 96-105, 2012. First published October 27, 2011 doi:10.1152/japplphysiol.00690.2011Spinal cord hemisection at C2 (C2HS) severs bulbospinal inputs to ipsilateral phrenic motoneurons causing transient hemidiaphragm paralysis. The spontaneous crossed-phrenic phenomenon (sCPP) describes the spontaneous recovery of ipsilateral phrenic bursting following C2HS. We reasoned that the immediate (next breath) changes in tidal volume (VT) induced by ipsilateral phrenicotomy during spontaneous breathing would provide a quantitative measure of the contribution of the sCPP to postinjury VT. Using this approach, we tested the hypothesis that the sCPP makes more substantial contributions to VT when respiratory drive is increased. Pneumotachography was used to measure VT in anesthetized, spontaneously breathing adult male rats at intervals following C2HS. A progressive increase in VT (ml/breath) occurred over an 8 wk period following C2HS during both poikilocapnic baseline breathing and hypercapnic respiratory challenge (7% inspired CO2). The sCPP did not impact baseline breathing at 1-3 days postinjury since VT was unchanged after ipsilateral phrenicotomy. However, by 2 wk post-C2HS, baseline phrenicotomy caused a 16 Ϯ 2% decline in VT; a comparable 16 Ϯ 4% decline occurred at 8 wk. Contrary to our hypothesis, the phrenicotomy-induced declines in VT (%) during hypercapnic respiratory stimulation did not differ from the baseline response at any postinjury time point (all P Ͼ 0.11). We conclude that by 2 wk post-C2HS the sCPP makes a meaningful contribution to VT that is similar across different levels of respiratory drive. plasticity; hemisection; phrenicotomy; cervix SEVERING IPSILATERAL BULBOSPINAL inputs to phrenic motoneurons via lateral hemisection of the C2 spinal cord (C2HS) transiently paralyzes the hemidiaphragm (22,23,27,48). However, a partial return of ipsilateral phrenic motoneuron inspiratory bursting occurs over a period of weeks to months following C2HS (14,15,20,37). This response has been termed the spontaneous crossed-phrenic phenomenon (sCPP; Refs. 22,28,40). The sCPP provides an important experimental model of neuroplasticity and associated functional recovery (i.e., phrenic bursting) after spinal cord injury (22,28,40). However, the functional contribution of the sCPP to ventilation (V E) has not been definitively established. In other words, it is unclear if the relatively small amount of electrical activity that has been measured in the ipsilateral phrenic nerve after chronic C2HS is sufficient to alter inspiratory tidal volume (V T ). Thus it is unknown if C2HS-induced, spontaneous neuroplastic changes associated with the sCPP (22, 23) have a meaningful impact on the respiratory system (20).The functional impact of the sCPP has been examined to a limited extent (14,15,20). Correlations between phrenic nerve activity ...

show abstract

Evolution and Functional Differentiation of the Diaphragm Muscle of Mammals

Fogarty¹,

Sieck²

2019

Comprehensive Physiology

View full text Add to dashboard Cite

Symmorphosis is a concept of economy of biological design, whereby structural properties are matched to functional demands. According to symmorphosis, biological structures are never over designed to exceed functional demands. Based on this concept, the evolution of the diaphragm muscle (DIAm) in mammals is a tale of two structures, a membrane that separates and partitions the primitive coelomic cavity into separate abdominal and thoracic cavities and a muscle that serves as a pump to generate intra-abdominal (P ab ) and intra-thoracic (P th ) pressures. The DIAm partition evolved in reptiles from folds of the pleural and peritoneal membranes that was driven by the biological advantage of separating organs in the larger coelomic cavity into separate thoracic and abdominal cavities, especially with the evolution of aspiration breathing. The DIAm pump evolved from the advantage afforded by more effectively generation of both a negative P th for ventilation of the lungs and a positive P ab for venous return of blood to the heart and expulsive behaviors such as airway clearance, defecation, micturition, and child birth. Didactic SynopsisThe DIAm separates abdominal and thoracic cavities; thus, it is a partition, and its evolution reflects that important role in isolating organs into separate thoracic and abdominal cavities. However, the DIAm is also a muscle, and is most often described as the principal pump muscle of inspiration. However, the DIAm also serves as a pump for generating both negative P th and positive P ab in other motor behaviors. Accordingly, the evolution of the DIAm is more complex and should be considered in the context of its dual physiological roles as a partition and muscular pump. In considering DIAm evolution, we adopt the guiding concept of symmorphosis or economy of design, where biological structures are not over designed for their functional roles. Thus, this is a tale of the evolution of two diaphragms, a partition and a muscular pump that separates thoracic and abdominal cavities but also affects generation of P th and P ab .

show abstract

Long-term facilitation of ipsilateral but not contralateral phrenic output after cervical spinal cord hemisection

Cited by 47 publications

References 27 publications

Phrenicotomy alters phrenic long-term facilitation following intermittent hypoxia in anesthetized rats

Phrenicotomy alters phrenic long-term facilitation following intermittent hypoxia in anesthetized rats

Contribution of the spontaneous crossed-phrenic phenomenon to inspiratory tidal volume in spontaneously breathing rats

Evolution and Functional Differentiation of the Diaphragm Muscle of Mammals

Contact Info

Product

Resources

About