Functional Connection From the Surface Chemosensitive Region to the Respiratory Neuronal Network in the Rat Medulla

  • Yasumasa Okada
  • Zibin Chen
  • Wuhan Jiang
  • Shun-ichi Kuwana
  • Frederic L. Eldridge
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 551)


Although the ventral medullary surface (VMS) has previously been assumed to be the main site for central respiratory chemoreception in mammals, it has recently been argued that chemosensitive sites are widespread in the lower brainstem, including the deep medullary regions1, 2, 3 (also see the reviews4, 5, 6). However, c-fos immunocytological studies have shown that CO2-activated cells are primarily located in the superficial ventral medulla.7, 8, 9 We have also recently suggested that the small cells surrounding fine vessels in the most superficial layer of the ventral medulla are the CO2 chemoreceptor cells.10 We also assume that there must be a neural connection from the VMS to the respiratory rhythm and pattern generating neuronal network, e.g., to the ventral respiratory group (VRG) region of the medulla. Here we analyze the respiratory output responses to local electrical or chemical stimulation at various sites in the VMS to establish a functional connection from the VMS to the respiratory neuronal network.


Functional Connection Chemical Stimulation Ventral Respiratory Group Ventral Medulla Gallamine Triethiodide 
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. 1.
    E. L. Coates, A. Li, and E. E. Nattie, Widespread sites of brain stem ventilatory chemoreceptors, J. Appl. Physiol. 75, 5–14 (1993).PubMedGoogle Scholar
  2. 2.
    E. E. Nattie, and A. Li, Central chemoreception in the region of the ventral respiratory group in the rat, J. Appl. Physiol. 81, 1987–1995 (1996).PubMedGoogle Scholar
  3. 3.
    C. Solomon, N. H. Edelman, and M. H. O’Neal 3rd., CO2/H+ chemoreception in the cat pre-Bötzinger complex in vivo, J. Appl. Physiol. 88, 1996–2007 (2000).PubMedGoogle Scholar
  4. 4.
    H. H. Loeschcke, Central chemosensitivity and the reaction theory, J. Physiol. (Lond.) 332, 1–24 (1982).Google Scholar
  5. 5.
    D. E. Millhorn, and F. L. Eldridge, Role of ventrolateral medulla in regulation of respiratory and cardiovascular systems, J. Appl. Physiol. 61, 1249–1263 (1986).PubMedGoogle Scholar
  6. 6.
    Y. Okada, Z. Chen Z, and S. Kuwana, Cytoarchitecture of central chemoreceptors in the mammalian ventral medulla, Respir. Physiol. 129,13–23 (2001).CrossRefPubMedGoogle Scholar
  7. 7.
    M. Sato, J. W. Severinghaus, and A. I. Basbaum, Medullary CO2 chemoreceptor neuron identification by c-fos immunocytochemistry, J. Appl. Physiol. 73, 96–100 (1992).PubMedGoogle Scholar
  8. 8.
    N. Larnicol, F. Wallois, P. Berquin, F. Gros, and D. Rose, C-fos-like immunoreactivity in the cat’s neuraxis following moderate hypoxia or hypercapnia, J. Physiol. (Paris) 88, 81–88 (1994).CrossRefGoogle Scholar
  9. 9.
    L. J. Teppema, J. G. Veening, A. Kranenburg, A. Dahan, A. Berkenbosch, and C. Olievier, Expression of c-fos in the rat brainstem after exposure to hypoxia and to normoxic and hyperoxic hypercapnia. J. Comp. Neurol. 388, 169–190 (1997).CrossRefPubMedGoogle Scholar
  10. 10.
    Y. Okada, Z. Chen, W. Jiang, S. Kuwana, and F. L. Eldridge, Anatomical arrangement of hypercapnia-activated cells in the superficial ventral medulla of rats, J. Appl. Physiol. 93, 427–439 (2002).PubMedGoogle Scholar
  11. 11.
    Z. Chen, J. Hedner, and T. Hedner, Substance P-induced respiratory excitation is blunted by delta-receptor specific opioids in the rat medulla oblongata, Acta Physiol. Scand. 157, 165–173 (1996).CrossRefPubMedGoogle Scholar
  12. 12.
    Y. Okada, A. Kawai, K. Mückenhoff, and P. Scheid, Role of the pons in hypoxic respiratory depression in the neonatal rat, Respir. Physiol. 111, 55–63 (1998).CrossRefPubMedGoogle Scholar
  13. 13.
    S. Kuwana, Y. Okada, and T. Natsui, Effects of extracellular calcium and magnesium on central respiratory control in the brainstem-spinal cord of neonatal rat, Brain Res. 786, 194–204 (1998).CrossRefPubMedGoogle Scholar
  14. 14.
    Y. Okada, K. Mückenhoff, G. Holtermann, H. Acker, and P. Scheid, Depth profiles of pH and PO2 in the isolated brain stem-spinal cord of the neonatal rat, Respir. Physiol. 93, 315–326 (1993).CrossRefPubMedGoogle Scholar
  15. 15.
    P. G. Wagner, and F. L. Eldridge, Development of short-term potentiation of respiration, Respir. Physiol. 83, 129–139 (1991).CrossRefPubMedGoogle Scholar
  16. 16.
    H. H. Loeschcke, J. de Lattre, M. E. Schläfke, and C. O. Trouth, Effects on respiration and circulation of electrically stimulating the ventral surface of the medulla oblongata, Respir. Physiol. 10, 184–197 (1970).CrossRefPubMedGoogle Scholar
  17. 17.
    J. L. Malcolm, I. H. Sarelius, and J. D. Sinclair, The respiratory role of the ventral surface of the medulla studied in the anaesthetized rat, J. Physiol. (Lond.) 307, 503–515 (1980).Google Scholar
  18. 18.
    C. O. Trouth, H. H. Loeschcke, and J. Berndt, Topography of the respiratory responses to electrical stimulation in the medulla oblongata, Pflügers Arch. 339, 153–170 (1973).CrossRefPubMedGoogle Scholar
  19. 19.
    M. E. Schlaefke, W. R. See, and H. H. Loeschcke, Ventilatory response to alterations of H+ ion concentration in small areas of the ventral medullary surface, Respir. Physiol. 10, 198–212 (1970).CrossRefPubMedGoogle Scholar
  20. 20.
    F. G. Issa, and J. E. Remmers, Identification of a subsurface area in the ventral medulla sensitive to local changes in PCO2, J. Appl. Physiol. 72, 439–446 (1992).PubMedGoogle Scholar
  21. 21.
    C. C. McIntyre, and W. M. Grill, Finite element analysis of the current-density and electric field generated by metal microelectrodes, Ann. Biomed. Eng. 29, 227–235 (2001).CrossRefPubMedGoogle Scholar
  22. 22.
    C. A. Connelly, H. H. Ellenberger, and J. L. Feldman, Are there serotonergic projections from raphe and retrotrapezoid nuclei to the ventral respiratory group in the rat?, Neurosci. Lett. 105, 34–40 (1989).CrossRefPubMedGoogle Scholar
  23. 23.
    H. H. Ellenberger, and J. L. Feldman, Origins of excitatory drive within the respiratory network: anatomical localization, Neuroreport 5, 1933–1936 (1994).CrossRefPubMedGoogle Scholar
  24. 24.
    L. Grelot, A. L. Bianchi, S. Iscoe, and J. E. Remmers, Expiratory neurones of the rostral medulla: anatomical and functional correlates, Neurosci. Lett. 89, 140–145 (1988).CrossRefPubMedGoogle Scholar
  25. 25.
    A. Kawai, D. Ballantyne, K. Mückenhoff, and P. Scheid, Chemosensitive medullary neurones in the brainstem-spinal cord preparation of the neonatal rat, J. Physiol. (Lond.) 492, 277–292 (1996).Google Scholar

Copyright information

© Kluwer Academic/Plenum Publishers, New York 2004

Authors and Affiliations

  • Yasumasa Okada
    • 1
  • Zibin Chen
    • 2
  • Wuhan Jiang
    • 3
  • Shun-ichi Kuwana
    • 4
  • Frederic L. Eldridge
    • 5
  1. 1.Department of MedicineKeio University Tsukigase Rehabilitation CenterIzu-City, Shizuoka-kenJapan
  2. 2.Department of Biochemical and Analytical PharmacologyGlaxoSmithKlineUSA
  3. 3.Lineberger Cancer CenterUniversity of North CarolinaChapel HillUSA
  4. 4.Department of PhysiologyTeikyo UniversityTokyoJapan
  5. 5.Department of Cell and Molecular PhysiologyUniversity of North CarolinaChapel HillUSA

Personalised recommendations