Phylogeny of vertebrate respiratory rhythm generators: The Oscillator Homology Hypothesis

Wilson, Richard J. A.; Vasilakos, Konstantinon; Remmers, John E.

doi:10.1016/j.resp.2006.04.007

Cited by 40 publications

(35 citation statements)

References 71 publications

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“…Intriguing proposals on the homology between oscillators in mammals and lower vertebrates have been advanced despite the insufficiency of available supporting data (Wilson et al, 2006). In agreement with Kinkead (2009), we believe that the lamprey pTRG displays a high homology not only with the mammalian preBötC, but also with the neural mechanisms generating lung ventilation in amphibians (Wilson et al, 2002;Vasilakos et al, 2005;Chen and Hedrick, 2008;Kottick et al, 2013) and turtles (Johnson et al, 2002(Johnson et al, , 2007, rather than with those that generate gill respiration in tadpoles (Galante et al, 1996;Broch et al, 2002).…”

Section: Evolutionary Conserved Characteristics Of the Respiratory Cpgsupporting

confidence: 82%

“…These latter, along with spinal motor nuclei innervating the intercostal muscles and diaphragm, progressively acquire a prominent respiratory role. These changes in the location of the respiratory CPG obviously imply a caudal migration of the original rhythm generating mechanism or the development of a new respiratory oscillator or multiple oscillators, entrained to a large degree (Wilson et al, 2002(Wilson et al, , 2006Vasilakos et al, 2005;Taylor et al, 2010;Kottick et al, 2013). The respiratory CPG of higher vertebrates and mammals remains placed in a cranial strategic position to drive close brainstem motoneurons that have to be engaged in advance and to send excitatory projections to lower respiratory muscles innervated by spinal motoneurons.…”

Section: Considerations On the Evolutionary Trends In Respiratory Rhymentioning

confidence: 99%

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Neural mechanisms underlying respiratory rhythm generation in the lamprey

Bongianni

Mutolo

Cinelli

et al. 2016

Respiratory Physiology & Neurobiology

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a b s t r a c tThe isolated brainstem of the adult lamprey spontaneously generates respiratory activity. The paratrigeminal respiratory group (pTRG), the proposed respiratory central pattern generator, has been anatomically and functionally characterized. It is sensitive to opioids, neurokinins and acetylcholine. Excitatory amino acids, but not GABA and glycine, play a crucial role in the respiratory rhythmogenesis. These results are corroborated by immunohistochemical data. While only GABA exerts an important modulatory control on the pTRG, both GABA and glycine markedly influence the respiratory frequency via neurons projecting from the vagal motoneuron region to the pTRG. Noticeably, the removal of GABAergic transmission within the pTRG causes the resumption of rhythmic activity during apnea induced by blockade of glutamatergic transmission. The same result is obtained by microinjections of substance P or nicotine into the pTRG during apnea. The results prompted us to present some considerations on the phylogenesis of respiratory pattern generation. They may also encourage comparative studies on the basic mechanisms underlying respiratory rhythmogenesis of vertebrates.

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Section: Evolutionary Conserved Characteristics Of the Respiratory Cpgsupporting

confidence: 82%

Section: Considerations On the Evolutionary Trends In Respiratory Rhymentioning

confidence: 99%

Neural mechanisms underlying respiratory rhythm generation in the lamprey

Bongianni

Mutolo

Cinelli

et al. 2016

Respiratory Physiology & Neurobiology

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“…46). One is located in the pre-Bötzinger complex (the locus of the putative I rhythm generator) (21,35,38), and the other is situated in the region of the retrotrapezoid nucleus and/or parafacial respiratory group, the proposed expiratory rhythm generator (18,19,31).…”

Section: Discussionmentioning

confidence: 99%

Uncoupling of upper airway motor activity from phrenic bursting by positive end-expired pressure in the rat

Lee¹,

Fuller²,

Tung³

et al. 2007

Journal of Applied Physiology

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Lee K-Z, Fuller DD, Tung L-C, Lu I-J, Ku L-C, Hwang J-C. Uncoupling of upper airway motor activity from phrenic bursting by positive end-expired pressure in the rat. J Appl Physiol 102: [878][879][880][881][882][883][884][885][886][887][888][889] 2007. First published November 2, 2006; doi:10.1152/japplphysiol.00934.2006.-Phasic bursting in the hypoglossal nerve can be uncoupled from phrenic bursting by application of positive end-expired pressure (PEEP). We wished to determine whether similar uncoupling can also be induced in other respiratory-modulated upper airway (UAW) motor outputs. Discharge of the facial, hypoglossal, superior laryngeal, recurrent laryngeal, and phrenic nerves was recorded in anesthetized, ventilated rats during stepwise changes in PEEP with a normocapnic, hyperoxic background. Application of 3-to 6-cmH 2O PEEP caused the onset inspiratory (I) UAW nerve bursting to precede the phrenic burst but did not uncouple bursting. In contrast, application of 9-to 12-cmH2O PEEP uncoupled UAW neurograms such that rhythmic bursting occurred during periods of phrenic quiescence. Single-fiber recording experiments were conducted to determine whether a specific population of UAW motoneurons is recruited during uncoupled bursting. The data indicate that expiratory-inspiratory (EI) motoneurons remained active, while I motoneurons did not fire during uncoupled UAW bursting. Finally, we examined the relationship between motoneuron discharge rate and PEEP during coupled UAW and phrenic bursting. EI discharge rate was linearly related to PEEP during preinspiration, but showed no relationship to PEEP during inspiration. Our results demonstrate that multiple UAW motor outputs can be uncoupled from phrenic bursting, and this response is associated with bursting of EI nerve fibers. The relationship between PEEP and EI motoneuron discharge rate differs during preinspiratory and I periods; this may indicate that bursting during these phases of the respiratory cycle is controlled by distinct neuronal outputs. uncoupled activity; motoneurons; expiratory-inspiratory; preinspiratory THE MAMMALIAN UPPER AIRWAY (UAW) consists of the airflow passages extending from the trachea to the external nares and is thus composed of the nasal cavity, pharynx, and larynx (34). The compliance and geometry of this region are influenced by a number of skeletal muscles. Among them are the alae nasi, tongue, and laryngeal muscles, which are innervated by the facial (FN), hypoglossal (HN) and superior (SLN), and recurrent laryngeal nerves (RLN), respectively (1,26,41).Many studies have shown that the inspiratory (I) discharge of the HN precedes the phrenic I burst (5,6,13,17,23,33). This preinspiratory (Pre-I) activity has been suggested to benefit UAW patency by dilating and stiffening the UAW before the onset of I airflow (30). Similar to the HN, the onset of FN, SLN, and RLN I bursting occurs before the onset of phrenic bursting (16,25).The respiratory-related discharge of the UAW muscles is influenced by various chemical and mechanical ...

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“…Such a pacemakers handshake process, therefore, provides an advantageous fail-safe mechanism that may sustain or augment breathing should the preBötC be insufficient or fail. We suggest that such fail-safe redundancy in pacemakers network design may be evolutionarily conserved with possible heritage from early ancestors, such as frogs and fish (57). When the pFRG excitability is partially restored (E Leak-pFRG ϭ Ϫ63.2 mV) the driving preBö tC burst may induce PIR of the pFRG which, in turn, triggers a second preBö tC burst in the absence of post-I inhibition of the preBö tC.…”

Section: Implications Of Pacemakers Handshake Modelmentioning

confidence: 94%

Pacemakers handshake synchronization mechanism of mammalian respiratory rhythmogenesis

Wittmeier

Song

Duffin

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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Inspiratory and expiratory rhythms in mammals are thought to be generated by pacemaker-like neurons in 2 discrete brainstem regions: pre-Bö tzinger complex (preBö tC) and parafacial respiratory group (pFRG). How these putative pacemakers or pacemaker networks may interact to set the overall respiratory rhythm in synchrony remains unclear. Here, we show that a pacemakers 2-way ''handshake'' process comprising pFRG excitation of the preBö tC, followed by reverse inhibition and postinhibitory rebound (PIR) excitation of the pFRG and postinspiratory feedback inhibition of the preBö tC, can provide a phase-locked mechanism that sequentially resets and, hence, synchronizes the inspiratory and expiratory rhythms in neonates. The order of this handshake sequence and its progression vary depending on the relative excitabilities of the preBö tC vs. the pFRG and resultant modulations of the PIR in various excited and depressed states, leading to complex inspiratory and expiratory phase-resetting behaviors in neonates and adults. This parsimonious model of pacemakers synchronization and mutual entrainment replicates key experimental data in vitro and in vivo that delineate the developmental changes in respiratory rhythm from neonates to maturity, elucidating their underlying mechanisms and suggesting hypotheses for further experimental testing. Such a pacemakers handshake process with conjugate excitation-inhibition and PIR provides a reinforcing and evolutionarily advantageous fail-safe mechanism for respiratory rhythmogenesis in mammals.entrainment ͉ parafacial respiratory group ͉ postinhibitory rebound ͉ preBö tzinger complex ͉ rhythm P acemaker bursting and beating are profound emergent behaviors at the single-cell level that are fundamental to a myriad of biological rhythms (1, 2). How distinct oscillators may synchronize at the network level to produce an ensemble rhythm in unison is an important question for many periodic phenomena in nature (3-5). In mammalian respiration, pacemaker-like neurons have been identified in 2 discrete regions in the rostral ventrolateral medulla (VLM): the pre-Bötzinger complex (preBötC) (6) and parafacial respiratory group (pFRG) (7-9). The demonstrated plurality of respiratory-related pacemakers has led to divergent hypotheses regarding the mechanism of respiratory rhythmogenesis in mammals: (i) the preBötC and pFRG rhythmogenic populations represent coupled inspiratory and expiratory rhythm generators (IRG, ERG) that separately drive inspiration and expiration (10-13); and (ii) pFRG neurons represent the master rhythm generator that not only sets the expiratory rhythm but also entrains inspiratory bursts (9,14).Both hypotheses appear to be well-founded and supported by relevant experimental data. Yet, both leave major questions unanswered. For one, how can the IRG and ERG synchronize without a master rhythm generator? Conversely, if the pFRG is a master rhythm generator, then why does breathing persist after its lesioning (9, 15)?To resolve the dilemma, we propose a mathematical model...

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Phylogeny of vertebrate respiratory rhythm generators: The Oscillator Homology Hypothesis

Cited by 40 publications

References 71 publications

Neural mechanisms underlying respiratory rhythm generation in the lamprey

Neural mechanisms underlying respiratory rhythm generation in the lamprey

Uncoupling of upper airway motor activity from phrenic bursting by positive end-expired pressure in the rat

Pacemakers handshake synchronization mechanism of mammalian respiratory rhythmogenesis

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