Models of Neuronal Bursting Behavior: Implications for In-Vivo Versus In-Vitro Respiratory Rhythmogenesis

  • Ilya A. Rybak
  • Walter M. St John
  • Julian F. R. Paton
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 499)


Neonatal in-vitro preparations can generate respiratory-like oscillations based on the intrinsic bursting or pacemaker properties in some neurons within the medullary preBötzinger complex (PBC)1-3. This discovery provided a basis for a hybrid pacemaker-network theory that suggests that pacemaker PBC neurons form a kernel of the central pattern generator and hence provide a necessary contribution to the genesis of the respiratory rhythm4. However, it is controversial whether a pacemaker-based mechanism necessarily operates in vivo. Specifically, the pacemaker-based models face principal problems in providing explanations to systems-level phenomena such as an independent regulation of respiratory phases, respiratory reflexes (e.g. the Hering-Breuer reflex), various phase resetting phenomena. On the other hand, the network theories and models based on in-vivo data can explain these phenomena5,6, but demand the respiratory phase transitions to be based on the reciprocal inhibitory interactions between respiratory neurons. Therefore, the network-based models have so far been unable to explain a pacemaker-driven rhythm recorded in vitro which is resistant to blockade of synaptic inhibition7. The current state of knowledge in the field requires a comprehensive computational study of the relationships between in-vivo and in-vitro data. The objective of this study was to explore the concept that the respiratory network can generate a breathing pattern by either a network or a hybrid pacemaker-network mechanism, which is state-dependent.


Respiratory Rhythm Respiratory Neuron Tonic Firing Pacemaker Neuron Excitatory Drive 
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  1. 1.
    S. M. Johnson, J. C. Smith, G. D. Funk, and J. L. Feldman, Pacemaker behavior of respiratory neurons in medullary slices from neonatal rat. J. Neurophysiol. 72, 2598–2608 (1994).PubMedGoogle Scholar
  2. 2.
    N. Koshiya and J. C. Smith, Neuronal pacemaker for breathing visualized in vitro. Nature 400 (6742), 360363 (1999).Google Scholar
  3. 3.
    J. C. Smith, H. Ellenberger, K. Ballanyi, D. W. Richter, and J. L. Feldman, Pre-Bötzinger complex: a brain stem region that may generate respiratory rhythm in mammals. Science 254, 726–729 (1991).PubMedCrossRefGoogle Scholar
  4. 4.
    J. C. Smith, in: Neurons, Networks, and Motor Behavior, edited by P. Stain, S. Grillner, A. I. Selverston, and D. G. Stuart (MIT Press, Cambridge, MA, 1997), pp. 97–104.Google Scholar
  5. 5.
    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).PubMedGoogle Scholar
  6. 6.
    I. A. Rybak, J. F. R. Paton, and J. S. Schwaber, Modeling neural mechanisms for genesis of respiratory rhythm and pattern: III. Comparison of model performances during afferent nerve stimulation, J. Neurophysiol. 77,2027–2039 (1997).PubMedGoogle Scholar
  7. 7.
    X. M. Shao and J. L. Feldman, Respiratory rhythm generation and synaptic inhibition of expiratory neurons in pre-Bötzinger complex: differential roles of glycinergic and gabaergic neural transmission, J. Neurophysiol. 77,1853–1860 (1997).PubMedGoogle Scholar
  8. 8.
    R. J. Butera, J. R. Rinzel, and J. C. Smith, Models of respiratory rhythm generation in the pre-Bötzinger complex: I. Bursting pacemaker neurons, J. Neurophysiol. 82, 382–397 (1999).Google Scholar
  9. 9.
    C. R. French, P. Sah, K. J. Buckett, and P. W. Gage, A voltage-dependent persistent sodium current in mammalian hippocampal neurons, J. Gen. Physiol. 95, 1139–1157 (1990).PubMedCrossRefGoogle Scholar
  10. 10.
    E. Nattie, CO2, brainstem chemoreceptors and breathing, Progr. in Neurobiol. 59, 299–331 (1999).CrossRefGoogle Scholar
  11. 11.
    W. M. St.-John, Rostral medullary respiratory neuronal activity of decelebrated cats in eupnea, apneusis and gasping, Resp. Physiol. 116, 47–65 (1999).CrossRefGoogle Scholar
  12. 12.
    J. E. Melton, S. C. Kadia, Q. P. Yu, J. A. Neubauer, and N. H. Edelman, Respiratory and sympathetic activity during recovery from hypoxic depression and gasping in cats, J. Appl. Physiol. 80, 1940–1948 (1996).PubMedCrossRefGoogle Scholar
  13. 13.
    A. K. Hammarström and P. W. Gage, Inhibition of oxidative metabolism increases persistent sodium current in rat CA1 hippocampal neurons, J. Physiol. 510, 735–741 (1998).PubMedCrossRefGoogle Scholar
  14. 14.
    I. C. Solomon, N. H. Edelman, and J. A. Neubauer, Pre-Bötzinger complex functions as a central hypoxia chemosensor for respiration in vivo, J. Neurophysiol. 83, 2854–2868 (2000).PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2001

Authors and Affiliations

  • Ilya A. Rybak
    • 1
  • Walter M. St John
    • 2
  • Julian F. R. Paton
    • 3
  1. 1.School of Biomedical EngineeringScience and Health Systems, Drexel UniversityPhiladelphiaPAUSA
  2. 2.Department of PhysiologyDartmouth Medical SchoolLebanonUSA
  3. 3.Department of PhysiologySchool of Medical Sciences, University of BristolUK

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