The automatic ventilatory patterns of eupnea and gasping can be observed from the day of birth. In eupnea and gasping, the discharge patterns of neuronal and neural activities are fundamentally different. In adult rats and cats, a medullary region has been identified which is critical for the neurogenesis of gasping, but not eupnea. This """"""""gasping center"""""""" partially overlaps with regions, termed the """"""""pre-Botzinger"""""""" complex and """"""""Pre-I"""""""" region, which are reported to contain neurons whose discharge underlies rhythm generation in an in vitro preparation of the neonatal rat. The """"""""gasping center"""""""", """"""""pre-Botzinger"""""""" complex and """"""""Pre- I"""""""" region may represent a continuous functional unit. This hypothesis is supported by the identity of the rhythmic activity of the in vitro preparation with gasping of in vivo neonatal rats. Moreover, in these neonatal animals, destruction of neurons in the various medullary regions eliminates gasping, but does not alter eupnea. The roles of medullary neuronal activities in the neurogenesis of eupnea and gasping will be assessed. The mechanisms will be evaluated by which these medullary neuronal activities underlying gasping are suppressed in eupnea. Specifically, the discharge of pontile neuronal activities is considered as the source of this suppression. In eupnea, pharmacological """"""""disinhibition"""""""" and/or excitation of medullary neuronal activities should result in gasping. The studies proposed will define the mechanisms whereby the dominance of the eupneic ventilatory rhythm is established. Results will provide a basis for understanding the failure of mechanisms for ventilatory neurogenesis, in apneas of neonates and adults.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL026091-17
Application #
2771235
Study Section
Respiratory and Applied Physiology Study Section (RAP)
Project Start
1982-01-01
Project End
2000-06-30
Budget Start
1998-09-01
Budget End
1999-08-31
Support Year
17
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Dartmouth College
Department
Physiology
Type
Schools of Medicine
DUNS #
041027822
City
Hanover
State
NH
Country
United States
Zip Code
03755
St-John, Walter M; Li, Aihua; Leiter, J C (2009) Genesis of gasping is independent of levels of serotonin in the Pet-1 knockout mouse. J Appl Physiol (1985) 107:679-85
St-John, Walter M; Stornetta, Ruth L; Guyenet, Patrice G et al. (2009) Location and properties of respiratory neurones with putative intrinsic bursting properties in the rat in situ. J Physiol 587:3175-88
St-John, Walter M (2008) Eupnea of in situ rats persists following blockers of in vitro pacemaker burster activities. Respir Physiol Neurobiol 160:353-6
St-John, Walter M; Leiter, J C (2008) Maintenance of gasping and restoration of eupnea after hypoxia is impaired following blockers of alpha1-adrenergic receptors and serotonin 5-HT2 receptors. J Appl Physiol 104:665-73
St-John, Walter M; Waki, Hidefumi; Dutschmann, Mathias et al. (2007) Maintenance of eupnea of in situ and in vivo rats following riluzole: a blocker of persistent sodium channels. Respir Physiol Neurobiol 155:97-100
Toppin, Veronica A L; Harris, Michael B; Kober, Anna M et al. (2007) Persistence of eupnea and gasping following blockade of both serotonin type 1 and 2 receptors in the in situ juvenile rat preparation. J Appl Physiol 103:220-7
Harris, Michael B; St-John, Walter M (2005) Phasic pulmonary stretch receptor feedback modulates both eupnea and gasping in an in situ rat preparation. Am J Physiol Regul Integr Comp Physiol 289:R450-R455
Pierrefiche, Olivier; Shevtsova, Natalia A; St-John, Walter M et al. (2004) Ionic currents and endogenous rhythm generation in the pre-Botzinger complex: modelling and in vitro studies. Adv Exp Med Biol 551:121-6
St-John, Walter M; Leiter, J C (2003) High-frequency oscillations of phrenic activity in eupnea and gasping of in situ rat: influence of temperature. Am J Physiol Regul Integr Comp Physiol 285:R404-12
Harris, Michael B; St -John, Walter M (2003) Tonic pulmonary stretch receptor feedback modulates both eupnea and gasping in an in situ rat preparation. Am J Physiol Regul Integr Comp Physiol 285:R215-21

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