The goal of this project is to define brain stem network mechanisms through which hypercapnia, carotid chemoreceptors, carotid baroreceptors, and cutaneous nociceptors shape the respiratory motor pattern. Multi-array recording technology, spike train analysis, and spike-triggered averaging of intracellular recordings will be used to measure the responses and functional associations of many neurons corded simultaneously in the medullary raphe nuclei, pontine respiratory group, and Botzinger-ventral respiratory group (BOT-VRG) of anesthetized or decerebrate artificially ventilated cats. Network models derived from these data will be tested with computer simulations. Planned experiments will address five hypotheses. Hypothesis 1; Pontine and medullary networks operate together to modulate the respiratory motor pattern in response to: a) brain stem hypercapnia (i.e., central chemoreception); b) carotid chemoreceptor stimulation, c) carotid baroreceptor stimulation, and d) cutaneous nociceptor stimulation. Hypothesis 2: Multiple reflex systems share pontomedullary networks in the regulation of the respiratory motor pattern. Hypothesis 3: Pontomedullary networks include internal checks and balances that regulate the duration and magnitude of carotid chemoreceptor and baroreceptor reflex actions on breathing. Hypothesis 4: Baroreceptor reflex actions in pontomedullary networks modulate nociceptive reflex actions on breathing. Hypothesis 5: Reflexively induced transient and long-term configurations of pontomedullary networks generate spatiotemporal patterns of synchrony, not apparent in conventional measures of firing rate, that act on the BOT-VRG. Improved treatments and management of disorders of respiratory and cardiovascular control depend on improved understanding of the neural system that regulates these functions. This project will complement advances currently being made with other in vivo and in vitro reductionistic approaches and identify network sites and processes where inherited or acquired abnormalities could disrupt breathing.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS019814-16
Application #
6165396
Study Section
Respiratory and Applied Physiology Study Section (RAP)
Program Officer
Chiu, Arlene Y
Project Start
1984-04-01
Project End
2003-02-28
Budget Start
2000-03-01
Budget End
2001-02-28
Support Year
16
Fiscal Year
2000
Total Cost
$367,588
Indirect Cost
Name
University of South Florida
Department
Physiology
Type
Schools of Medicine
DUNS #
City
Tampa
State
FL
Country
United States
Zip Code
33612
Lindsey, Bruce G; Nuding, Sarah C; Segers, Lauren S et al. (2018) Carotid Bodies and the Integrated Cardiorespiratory Response to Hypoxia. Physiology (Bethesda) 33:281-297
Nuding, Sarah C; Segers, Lauren S; Iceman, Kimberly E et al. (2015) Functional connectivity in raphé-pontomedullary circuits supports active suppression of breathing during hypocapnic apnea. J Neurophysiol 114:2162-86
Segers, L S; Nuding, S C; Ott, M M et al. (2015) Peripheral chemoreceptors tune inspiratory drive via tonic expiratory neuron hubs in the medullary ventral respiratory column network. J Neurophysiol 113:352-68
O'Connor, Russell; Segers, Lauren S; Morris, Kendall F et al. (2012) A joint computational respiratory neural network-biomechanical model for breathing and airway defensive behaviors. Front Physiol 3:264
Morris, K F; Nuding, S C; Segers, L S et al. (2010) Respiratory and Mayer wave-related discharge patterns of raphe and pontine neurons change with vagotomy. J Appl Physiol 109:189-202
Dick, Thomas E; Baekey, David M; Paton, Julian F R et al. (2009) Cardio-respiratory coupling depends on the pons. Respir Physiol Neurobiol 168:76-85
Dick, Thomas E; Shannon, Roger; Lindsey, Bruce G et al. (2008) Pontine respiratory-modulated activity before and after vagotomy in decerebrate cats. J Physiol 586:4265-82
Lindsey, Bruce G; Gerstein, George L (2006) Two enhancements of the gravity algorithm for multiple spike train analysis. J Neurosci Methods 150:116-27
Dick, Thomas E; Shannon, Roger; Lindsey, Bruce G et al. (2005) Arterial pulse modulated activity is expressed in respiratory neural output. J Appl Physiol 99:691-8
Dick, Thomas E; Morris, Kendall F (2004) Quantitative analysis of cardiovascular modulation in respiratory neural activity. J Physiol 556:959-70

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