Ventilatory activity can be generated at multiple brainstem sites. Gasping is recorded following the isolation of medulla from pons. A region of the lateral tegmental field is hypothesized to contain the central pattern generator for gasping, which contains pacemaker elements. Studies will evaluate further these hypotheses by characterizing the neuronal activities and afferent and efferent projections from this region. Evaluations of gasping may provide insights into the neurogenesis of all patterns of automatic ventilatory activity. Even if pacemaker elements do underlie ventilatory neurogenesis, neuronal circuits define the phasic periods of inspiration and expiration and shape respiratory-modulated neural discharge patterns. In this context, neurons of the rostral pontile """"""""pneumotaxic center"""""""" exercise multiple functions in ventilatory control and, possibly, neurogenesis. Such functions include the onset and terminations of inspiration, integration of central chemoreceptor afferent stimuli, and onset of spinal expiratory neural activities. The hypothesis will be evaluated that these multiple functions are regulated by different subpopulations within the pneumotaxic system. The question of subpopulations will also be examined in studies concerning the neural circuit which is responsible for the definition of expiratory activities. Recent evidence has demonstrated that neural expiration may be divided into two phases. A critical role in defining these phases is exercised by the discharge of post-inspiratory neurons. However, information concerning these neuronal activities is conflicting. This conflicting information may reflect the existence of subpopulations. The hypothesis will be evaluated that some post-inspiratory neurons are premotor to pharyngeal or laryngeal motoneurons whereas others are involved in the definition of expiratory activity for the entire ventilatory control system. The final studies will characterize a neuronal circuit which is critical only for expiratory activities of spinal nerves. This circuit, involving the infracerebellar nucleus of the cerebellum, is hypothesized to regulate spinal motonueronal activities by a pathway which bypasses the medullary respiratory nuclei. Activity within this circuit may provide an explanation for several enigmas concerning the regulation of spinal expiratory activities, including the influence of posture and the elimination of these activities, but not those of bulbospinal expiratory neurons, in anesthesia.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL026091-12
Application #
3338456
Study Section
Respiratory and Applied Physiology Study Section (RAP)
Project Start
1982-01-01
Project End
1995-12-31
Budget Start
1993-01-01
Budget End
1993-12-31
Support Year
12
Fiscal Year
1993
Total Cost
Indirect Cost
Name
Dartmouth College
Department
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; 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 (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; 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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