Abstract
It has been established that the normal respiratory pattern (“eupnoea”) in mammals is generated in the lower brainstem1,2 and may involve several medullary and pontine regions. Although some researchers suggest that a smaller region within the medulla (e.g., the pre-Bötzinger Complex (pre-BötC) may be sufficient for the respiratory rhythm generation3–5, the eupnoeic respiratory rhythm (as well as apneustic breathing) has never been reproduced in reduced medullary preparations without the pons. At the same time, the specific ponto-medullary interactions related to genesis, shaping and control of the respiratory pattern have not been well characterized so far. Here we present a preliminary computational model of the ponto-medullary respiratory network that is considered a basis for the future interactive modeling-experimental studies. The model has been developed using a series of assumptions. Specifically, we have suggested that, under normal conditions in vivo, the eupnoeic respiratory rhythm is generated by a ponto-medullary network. Hence, although the pre-BötC is a necessary part of this network, the intrinsic oscillations in this region are suppressed during eupnoea by ponto-medullary interactions. These endogenous oscillations, however, may be released under some specific conditions, e.g., in vitro, because of the lack of the pons, or during hypoxia in vivo 6. We have also assumed that the medullary part of the respiratory network contains special neural circuits performing the respiratory phase switching. Moreover, these circuits are also targets for pulmonary feedback and inputs from the pons and major afferent nerves, which use the same medullary switching circuits to regulate the timing of phase transitions and modulate the respiratory motor pattern7.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsPreview
Unable to display preview. Download preview PDF.
References
T. Lumsden, Observations on the respiratory centres in the cat, J. Physiol. Lond. 57, 153–160 (1923).
M. I. Cohen, Neurogenesis of respiratory rhythm in the mammal, Physiol. Rev. 59, 1105–1173 (1979).
J. C. Smith, H. H. Ellenberger, K. Ballanyi, D. W. Richter, and J. L. Feldman, Pre-Bötzinger complex: A brainstem region that may generate respiratory rhythm in mammals, Science 254, 726–729 (1991).
J. C. Rekling and J. L. Feldman, Pre-Bötzinger complex and pacemaker neurons: hypothesized site and kernel for respiratory rhythm generation, Ann. Rev. Physiol. 60, 385–405 (1998).
S. P. Lieske, M. Thoby-Brisson, P. Telgkamp, and J. M. Ramirez, Reconfiguration of the neural network controlling multiple breathing patterns: eupnea, sighs and gasps, Nature Neurosci. 3, 600–607 (2000).
W. M. St.-John, I. A. Rybak, and J. F. R. Paton, Potential switch from eupnea to fictive gasping after blockade of glycine transmission and potassium channels, Am. J. Physiol. (Integr. Comp. Physiol.) 283, R721–R731 (2002).
M. Okazaki, R. Takeda, H. Yamazaki, and A. Haji, Synaptic mechanisms of inspiratory off-switching evoked by pontine pneumotaxic stimulation in cats, Neurosci. Res. 44, 101–110 (2002).
D. W. Richter, Neural regulation of respiration: rhythmogenesis and afferent control. In: Comprehensive Human Physiology, edited by R. Gregor and U. Windhorst (Berlin: Springer-Verlag, 1996), vol. II, pp. 2079–2095.
A. Haji, M. Okazaki, H. Yamazaki, and R. Takeda, Physiological properties of late inspiratory neurons and their possible involvement in inspiratory off-switching in cats, J. Neurophysiol. 87, 1057–1067, (2001).
J. L. Feldman, Neurophysiology of breathing in mammals. In: Handbook of Physiology, edited by F. E. Bloom (Bethesda, MD: Am. Physiol. Soc., 1986), sec. 1, vol. 4, pp. 463–524.
E. E. Lawson, Prolonged central respiratory inhibition following reflex-induced apnea, J. Appl. Physiol. 50, 844–879 (1981).
J. E. Remmers, D. W. Richter, D. Ballantyne, C. R. Bainton, and J. P. Klein, Reflex prolongation of stage I of expiration, Pflügers Arch. 407, 190–198 (1986).
F. J. Clark and C. von. Euler, On the regulation of depth and rate of breathing, J. Physiol. Lond. 222, 267–295 (1972).
C. K. Knox, Characteristics of inflation and deinflation reflexes during expiration in the cat, J. Neurophysiol. 36, 284–295 (1973).
J. Jodkowski, S. Coles, and T. E. Dick, A ‘pneumotaxic centre’ in rats, Neurosci. Lett, 172, 67–72 (1994).
J. Jodkowski, S. Coles, and T. E. Dick, Prolongation in expiration evoked from ventrolateral pons of adult rats, J. Appl. Physiol. 82, 377–381 (1997).
S. F. Morrison, S. L. Cravo, and H. M. Wilfehrt, Pontine lesions produce apneusis in the rat, Brain Res. 652, 83–86 (1994).
W. M. St.-John, Neurogenesis of patterns of automatic ventilatory activity, Prog. Neurobiol. 56, 97–117 (1998).
J. H. Peever, J. H. Mateika, and J. Duffin, Respiratory control of hypoglossal motoneurones in the rat, Pflügers Arch. 442, 78–86 (2001).
I. A. Rybak, K. Ptak, N. A. Shevtsova, and D.R. McCrimmon, Sodium currents in neurons from the rostroventrolateral medulla of the rat, J. Neurophysiol. 90, 1635–1642 (2003).
F. P. Elsen and J. Ramirez, Calcium currents of rhythmic neurons recorded in the isolated respiratory network of neonatal mice, J. Neurosci. 18, 10652–10662 (1998).
D. Frermann, B. U. D. Keller, and D. W. Richter, Calcium oscillations in rhythmically active respiratory neurones in the brainstem of the mouse, J. Physiol. Lond. 515, 119–131 (1999).
I. A. Rybak, J. F. R. Paton, and J. S. Schwaber, Modeling neural mechanisms for genesis of respiratory rhythm and pattern: I. Models of respiratory neurons, J. Neurophysiol. 77, 1994–2006 (1997).
I. A. Rybak, J. F. R. Paton, and J. S. Schwaber, Modeling neural mechanisms for genesis of respiratory rhythm and pattern: II. Network models of the central respiratory pattern generator, J. Neurophysiol. 77, 2007–2026 (1997).
I. A. Rybak, N. A. Shevtsova, W. M. St.-John, J. F. R. Paton, and O. Pierrefiche, Endogenous rhythm generation in the pre-Bötzinger complex and ionic currents: Modelling and in vitro studies, Eur. J. Neurosci. 18, 239–257 (2003).
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2004 Kluwer Academic/Plenum Publishers, New York
About this paper
Cite this paper
Rybak, I.A., Shevtsova, N.A., Paton, J.F.R., Pierrefiche, O., St.-John, W.M., Haji, A. (2004). Modelling Respiratory Rhythmogenesis: Focus on Phase Switching Mechanisms. In: Champagnat, J., Denavit-Saubié, M., Fortin, G., Foutz, A.S., Thoby-Brisson, M. (eds) Post-Genomic Perspectives in Modeling and Control of Breathing. Advances in Experimental Medicine and Biology, vol 551. Springer, Boston, MA. https://doi.org/10.1007/0-387-27023-X_29
Download citation
DOI: https://doi.org/10.1007/0-387-27023-X_29
Publisher Name: Springer, Boston, MA
Print ISBN: 978-0-306-48507-7
Online ISBN: 978-0-387-27023-4
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)