Belt-and-Suspenders as a Biological Design Principle

  • Nicholas M. Mellen
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 605)

Recent studies have shown both the pFRG and the preBötC are sufficient to generate respiratory rhythm, and are hypothesized to do so via distinct mechanisms (Onimaru and Homma 2003; Mellen, Janczewski, Bocchiaro and Feldman 2003). The coexistence of mechanistically distinct, functionally matching networks (defined as degeneracy, Edelman and Gally 2001) is a ubiquitous feature of motor networks in both invertebrates (Selverston and Miller 1980) and vertebrates (DiDomenico, Nissanov and Eaton 1988). In almost all cases, a consensus exists about which subsystem is the “primary” rhythm generator, yet consistently, the effect of modulators on the isolated primary rhythm generator is qualitatively different than their effect on the more intact network (Ayali and Harris-Warrick 1999) and, in the intact animal, all rhythmogenic networks are active during motor pattern generation. Thus, at best, ascribing primacy to a particular network has weak support (since the other networks can produce qualitatively similar patterns; Prinz, Bucher and Marder 2004) and little explanatory power (since effects of modulatory inputs on the isolated “primary” rhythm generator do not persist in more intact networks). The ubiquity of degenerate networks for motor pattern generation suggests that a more useful question is why such an organization exists. We propose that degeneracy is ubiquitous because it reduces the phenotype's sensitivity to genetic mutation and environmental perturbation, and broadens the adaptiveness of motor patterns.


Respiratory Rhythm Rhythm Generator Pacemaker Neuron Respiratory Network Motor Pattern Generation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Becker, C.M., Hoch, W. et al. (1988) Glycine receptor heterogeneity in rat spinal cord during postnatal development. The EMBO Journal 7(12), 3717–3726.PubMedGoogle Scholar
  2. Butera, R.J., Jr., Rinzel, J. et al. (1999) Models of respiratory rhythm generation in the pre-Botzinger complex. I. Bursting pacemaker neurons. J. Neurophysiol. 82(1), 382–397.PubMedGoogle Scholar
  3. Butera, R.J., Jr., Rinzel, J. et al. (1999) Models of respiratory rhythm generation in the pre-Botzinger complex. II. Populations of coupled pacemaker neurons. J. Neurophysiol. 82(1), 398–415.PubMedGoogle Scholar
  4. Chatonnet, F., Borday, C. et al. (2006) Ontogeny of central rhythm generation in chicks and rodents. Respir. Physiol. Neurobiol. 154(1–2), 37–46.CrossRefPubMedGoogle Scholar
  5. Chatonnet, F., del Toro, E.D. et al. (2002) Different respiratory control systems are affected in homozygous and heterozygous kreisler mutant mice. Eur. J. Neurosci. 15(4), 684–692.CrossRefPubMedGoogle Scholar
  6. Del Negro, C.A., Morgado-Valle, C. et al. (2002) Respiratory rhythm: an emergent network property? Neuron. 34(5), 821–830.CrossRefPubMedGoogle Scholar
  7. del Toro, E.D., Borday, V. et al. (2001) Generation of a novel functional neuronal circuit in Hoxa1 mutant mice. J. Neurosci. 21(15), 5637–5642.PubMedGoogle Scholar
  8. Edelman, G.M. and Gally, J.A. (2001) Degeneracy and complexity in biological systems. Proc. Natl. Acad. Sci. USA 98(24), 13763–13768.CrossRefPubMedGoogle Scholar
  9. Feldman, J.L. and Janczewski, W.A. (2006) Point:Counterpoint: The parafacial respiratory group (pFRG)/pre-Botzinger complex (preBotC) is the primary site of respiratory rhythm generation in the mammal. Counterpoint: the preBotC is the primary site of respiratory rhythm generation in the mammal. J. Appl. Physiol. 100(6), 2096–2097 (discussion 2097–2099, 2103–2108).PubMedGoogle Scholar
  10. Kiecker, C. and Lumsden, A. (2005) Compartments and their boundaries in vertebrate brain development. Nat. Rev. Neurosci. 6(7), 553–564.CrossRefPubMedGoogle Scholar
  11. Leonardo, A. (2005) Degenerate coding in neural systems. J. Comp. Physiol. A Neuroethol. Sens. Neural. Behav. Physiol. 191(11), 995–1010.CrossRefPubMedGoogle Scholar
  12. Mellen, N.M., Janczewski, W.A. et al. (2003) Opioid-induced quantal slowing reveals dual networks for respiratory rhythm generation. Neuron 37(5), 821–826.CrossRefPubMedGoogle Scholar
  13. Mellen, N.M., Roham, M. et al. (2004) Afferent modulation of neonatal rat respiratory rhythm in vitro: cellular and synaptic mechanisms. J. Physiol. 556(Pt. 3), 859–874.CrossRefPubMedGoogle Scholar
  14. Onimaru, H., Arata, A. et al. (1989) Firing properties of respiratory rhythm generating neurons in the absence of synaptic transmission in rat medulla in vitro. Experimental Brain Research 76(3), 530–536.CrossRefGoogle Scholar
  15. Onimaru, H., Arata, A. et al. (1997) Neuronal mechanisms of respiratory rhythm generation: an approach using in vitro preparation. Jpn. J. Physiol. 47(5), 385–403.CrossRefPubMedGoogle Scholar
  16. Onimaru, H. and Homma, I. (2003). A novel functional neuron group for respiratory rhythm generation in the ventral medulla. J. Neurosci. 23(4), 1478–1486.PubMedGoogle Scholar
  17. Onimaru, H. and Homma, I. (2006) Point:Counterpoint: The parafacial respiratory group (pFRG)/pre-Botzinger complex (preBotC) is the primary site of respiratory rhythm generation in the mammal. Point: the PFRG is the primary site of respiratory rhythm generation in the mammal. J. Appl. Physiol. 100(6), 2094–2095.CrossRefPubMedGoogle Scholar
  18. Onimaru, H., Kumagawa, Y. et al. (2006) Respiration-related rhythmic activity in the rostral medulla of newborn rats. J. Neurophysiol. 96(1), 55–61.CrossRefPubMedGoogle Scholar
  19. Paton, J.F. and Richter, D.W. (1995) Role of fast inhibitory synaptic mechanisms in respiratory rhythm generation in the maturing mouse. J. Physiol. 484 (Pt. 2), 505–521.PubMedGoogle Scholar
  20. Pena, F., Parkis, M.A. et al. (2004) Differential contribution of pacemaker properties to the generation of respiratory rhythms during normoxia and hypoxia. Neuron 43(1), 105–117.CrossRefPubMedGoogle Scholar
  21. Ren, J. and Greer, J.J. (2006) Modulation of respiratory rhythmogenesis by chloride-mediated conductances during the perinatal period. J. Neurosci. 26(14), 3721–3730.CrossRefPubMedGoogle Scholar
  22. Straka, H., Baker, R. et al. (2002) The frog as a unique vertebrate model for studying the rhombomeric organization of functionally identified hindbrain neurons. Brain Res. Bull. 57(3–4), 301–305.Google Scholar
  23. Takeda, S., Eriksson, L.I. et al. (2001) Opioid action on respiratory neuron activity of the isolated respiratory network in newborn rats. Anesthesiology 95(3), 740–749.CrossRefPubMedGoogle Scholar
  24. Vasilakos, K., Wilson, R.J. et al. (2005) Ancient gill and lung oscillators may generate the respiratory rhythm of frogs and rats. J. Neurobiol. 62(3), 369–385.CrossRefPubMedGoogle Scholar
  25. Viemari, J.C., Burnet, H. et al. (2003) Perinatal maturation of the mouse respiratory rhythm-generator: in vivo and in vitro studies. Eur. J. Neurosci. 17(6), 1233–1244.CrossRefPubMedGoogle Scholar
  26. Wilson, R.J., Vasilakos, K. et al. (2006) Phylogeny of vertebrate respiratory rhythm generators: The oscillator homology hypothesis. Respir. Physiol. Neurobiol. 154(1–2), 47–60.CrossRefPubMedGoogle Scholar

Copyright information

© Springer 2008

Authors and Affiliations

  • Nicholas M. Mellen
    • 1
  1. 1.Kosair Children's Hospital Research InstituteUniversity of LouisvilleLouisvilleUSA

Personalised recommendations