The aims of the research activities proposed herein are twofold: 1) to evaluate the capacity for respiratory rhythm generation at multiple sites within the brainstem and, 2) to evaluate the neurophysiological underlying the ventilatory activity which may be supported by the bulbospinal portion of the central nervous system. In the context of the latter, we believe that examinations of bulbospinal respiratory rhythm generation will be fruitful since bulbospinal elements represent a potentially simpler respiratory controller and, by definition, an anatomically simpler entity than the entire pontile-bulbospinal complex. Experiments which will be conducted to fulfill the above two aims will have as one common objective, the reversible or permanent blockade of neural activity at the pontomedullary junction. Thus, by procedures to be described herein, respiratory patterns may be reversibly altered and segments of the brainstem and spinal cord reversibly isolated from other portions of the central nervous system. Respiratory-modulated activity within the """"""""isolated neural segments"""""""" will be monitored by recording activity in peripheral and/or cranial nerves and activity of single respiratory-modulated brainstem units. We believe that results of studies proposed herein will provide significant insights into the mechanisms responsible for the neurogenesis of automatic ventilatory activity.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL026091-07
Application #
3338452
Study Section
Respiratory and Applied Physiology Study Section (RAP)
Project Start
1982-01-01
Project End
1990-12-31
Budget Start
1988-01-01
Budget End
1988-12-31
Support Year
7
Fiscal Year
1988
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 (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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