Catecholaminergic Modulation of the Respiratory Rhythm Generator in the Isolated Brainstem—Spinal Cord Preparation from Neonatal Rat

  • Akiko Arata
  • Morimitsu Fujii
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 605)

The hypothesized respiratory rhythm generator is located in the neonatal medulla and consists of pre-inspiratory (Pre-I) neurons in the parafacial respiratory group (pFRG) (Onimaru and Homma 2003) and inspiratory (I) neurons in the pre-Botzinger complex (PBC) (Smith, Ellenberger, Ballanyi, Richter and Feldman 1991). The Pre-I neurons are thought to trigger firing of I neurons (Onimaru, Arata and Homma 1997) which, in turn, send axons to the inspiratory motor neurons in the spinal cord. The respiratory rhythm generator is controlled in part by inputs from the nucleus tractus solitarii (NTS). The NTS is the main relay of the Hering-Breuer reflex. Moreover, the NTS receives direct projections from the cerebral cortex and the limbic system, including the insular cortex. The NTS contains catecholaminergic neurons that project to the respiratory rhythm generator in the rostral ventrolateral medulla (RVLM). In rats, adrenaline-containing neurons of the RVLM, namely the C1 group, are primarily unilaterally innervated by neurons in the NTS. Reis and colleagues suggested that these neurons synapsing in or projecting through the C1 area mediate the baro- and cardiopulmonary mechanoreceptor reflex (Granata, Ruggiero, Park, Joh and Reis 1983). Dopamine antagonist administration in vivo attenuated ventilatory responses to hypoxia (Hsiao, Lahiri and Mokashi 1989), and direct dopamine application on the rat medulla—spinal cord preparation depressed respiratory frequency (Fujii, Umezawa and Arata 2004; 2006). Using the isolated medulla—spinal cord preparation and single-cell recordings, we investigated the cellular mechanisms of catecholaminergic respiratory regulation.


Nucleus Tractus Solitarii Respiratory Rhythm Respiratory Neuron Rostral Ventrolateral Medulla Respiratory Network 
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. Arata, A., Onimaru, H. and Homma, I. (1998) The adrenergic modulation of firings of respiratory rhythm generating neurons in medulla-spinal cord preparation from newborn rat. Exp. Brain Res. 119, 399–408.CrossRefPubMedGoogle Scholar
  2. Fujii, M., Umezawa, K. and Arata, A. (2004) Dopaminergic modulation on respiratory rhythm in rat brainstem-spinal cord preparation. Neurosci. Res. 50, 355–359.CrossRefPubMedGoogle Scholar
  3. Fujii, M., Umezawa, K. and Arata, A. (2006) Dopamine desynchronizes the pace-making neuronal activity of rat respiratory rhythm generation. Eur. J. Neurosci. 23, 1015–1027.CrossRefPubMedGoogle Scholar
  4. Granata, A.R., Ruggiero, D.A., Park, D.H., Joh, T.H. and Reis, D.J. (1983) Lesions of epinephrine neurons in the rostral ventrolateral medulla abolish the vasodepressor components of baroreflex and cardiopulmonary reflex. Hypertension 5, V80–84.PubMedGoogle Scholar
  5. Hsiao, C., Lahiri, S. and Mokashi, A. (1989) Peripheral and central dopamine receptors in respiratory control. Respir. Physiol. 76, 327–336.CrossRefPubMedGoogle Scholar
  6. Jurgens, U. (2002) Neural pathways underlying vocal control. Neurosci. Biobehav. Rev. 26, 235–258.CrossRefPubMedGoogle Scholar
  7. Kabotyanski, E.A., Baxter, D.A., Cushman, S.J. and Byrne, J.H. (2000) Modulation of fictive feeding by dopamine and serotonin in Aplysia. J. Neurophysiol. 83, 374–392.PubMedGoogle Scholar
  8. Mellen, N.M. and Feldman, J.L. (2000) Phasic lung inflation shortens inspiration and respiratory period in the lung-attached neonate rat brain stem spinal cord. J. Neurophysiol. 83, 3165–3168.PubMedGoogle Scholar
  9. Mitchell, R.A. and Berger, A.J. (1975) Neural regulation of respiration. Am. Rev. Respir. Dis. 111, 206–224.PubMedGoogle Scholar
  10. Murakoshi, T. and Otsuka, M. (1985) Respiratory reflexes in an isolated brainstem-lung preparation of the newborn rat: possible involvement of gamma-aminobutyric acid and glycine. Neurosci. Lett. 62, 63–68.CrossRefPubMedGoogle Scholar
  11. Onimaru, H., Arata, A. and Homma, I. (1997) Neuronal mechanisms of respiratory rhythm generation: an approach using in vitro preparation. Jpn. J. Physiol. 47, 385–403.CrossRefPubMedGoogle Scholar
  12. Onimaru, H. and Homma, I. (2003) A novel functional neuron group for respiratory rhythm generation in the ventral medulla. J. Neurosci. 23, 1478–1486.PubMedGoogle Scholar
  13. Smith, J.C., Ellenberger, H.H., Ballanyi, K., Richter, D.W. and Feldman, J.L. (1991) Pre-Botzinger complex: a brainstem region that may generate respiratory rhythm in mammals. Science 254, 726–729.CrossRefPubMedGoogle Scholar
  14. Smith, J.C., Ballanyi, K. and Richter, D.W. (1992) Whole-cell patch-clamp recordings from respiratory neurons in neonatal rat brainstem in vitro. Neurosci. Lett. 134, 153–156.CrossRefPubMedGoogle Scholar
  15. Suzue, T. (1984) Respiratory rhythm generation in the in vitro brainstem-spinal cord preparation of the neonatal rat. J. Physiol. (Lond) 354, 173–183.PubMedGoogle Scholar
  16. Svensson E, Woolley J, Wikstrom M, Grillner S. (2003) Endogenous dopaminergic modulation of the lamprey spinal locomotor network. Brain Res. 970:1–8.CrossRefPubMedGoogle Scholar

Copyright information

© Springer 2008

Authors and Affiliations

  • Akiko Arata
    • 1
  • Morimitsu Fujii
    • 1
  1. 1.Laboratory for Memory and LearningRIKEN Brain Science InstituteWakoJapan

Personalised recommendations