""""""""Automatic"""""""" breathing movements, which occur without conscious effort, are generated within the pontile and medullary portions of the brainstem. There are several patterns of """"""""automatic"""""""" ventilation. Eupnea is """"""""normal"""""""" breathing. In eupnea, sufficient oxygen is supplied to the body and carbon dioxide removed to meet metabolic demands. If eupnea ceases, hypoxia will develop. Severe hypoxia recruits gasping, which serves as a powerful defensive mechanism for """"""""autoresuscitation."""""""" A fundamental question concerns the specific neurophysiological mechanisms which generate eupnea and gasping. In severe hypoxia, it is hypothesized that a latent pacemaker discharge of medullary respiratory neurons is released to generate the gasp. In eupnea, this pacemaker activity is incorporated into the pontomedullary neuronal circuits responsible for the neurogenesis of eupnea. A definition of the neurophysiological processes responsible for this incorporation will enhance our understanding of the neurogenesis of eupnea, per se. The studies proposed require the reversible alteration of eupnea to gasping. Moreover, in order to evaluate the role of various putative neurotransmitters in ventilatory neurogenesis, pharmacological agents will be administered systemically, as well as onto neurons by microiontophoresis. The perfused """"""""juvenile rat"""""""" is uniquely suited for the successful performance of these studies. Since the systemic """"""""respiratory"""""""" and """"""""circulatory"""""""" systems of this preparation are """"""""replaced"""""""" by an extracorporeal circuit, there is no possibility of cardiac failure during hypoxia-induced gasping. Likewise, pharmacological agents can be administered which would almost certainly compromise cardiovascular function and viability of an in vivo preparation. Results of these studies will provide significant information into the mechanisms by which normal breathing is generated. Such information might provide insights into dysfunctions of the control of ventilation in humans, such as in """"""""sleep apneas"""""""" or the """"""""sudden infant death syndrome.""""""""

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Respiratory and Applied Physiology Study Section (RAP)
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Twery, Michael
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Dartmouth College
Schools of Medicine
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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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