Understanding the brainstem network that generates and modulates the respiratory motor pattern is an important goal in physiology and medicine. Disorders that disrupt breathing are associated with the development of pulmonary and systemic hypertension, sudden infant death, learning disabilities, Parkinson's disease and autonomic dysfunction, and other disorders and risks, e.g., stroke and multiple sclerosis. A neural network in the ventrolateral medulla is considered essential for generating the respiratory motor pattern. The circuits used by other brainstem sites to modulate this network are not known. The primary hypothesis of this project is: Peripheral and central chemoreceptors modulate the respiratory motor pattern through a distributed network that includes multifunctional neurons in the """"""""pontine respiratory group"""""""" (PRG), the medullary raphe nuclei, and the locus ceruleus. The project has four specific aims: 1. Define functional circuits within the pontine respiratory group (PRG) and between the PRG and the core medullary respiratory network. 2. Define the functional circuits of the PRG and the core medullary respiratory network appropriate for modulation of the respiratory motor pattern during changes in central and peripheral chemoreceptor drive. 3. Define the functional connectivity of raphe neurons that respond to changes in central and peripheral chemoreceptor drive, including functional circuits between the raphe system and the PRG and core medullary networks. 4. Identify functional circuits of locus ceruleus neurons that respond to changes in central and peripheral chemoreceptor drive and their functional connectivity with other modulatory domains and the core medullary respiratory network. The project will use multi-array recordings and computational methods to define functional circuits and their responses during chemoreceptor challenges that alter breathing. The results will lead to new network models of the respiratory brainstem in both normal and pathophysiological conditions.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37NS019814-25
Application #
7795680
Study Section
Respiratory Physiology Study Section (RESP)
Program Officer
Chen, Daofen
Project Start
1984-04-01
Project End
2011-08-31
Budget Start
2010-04-01
Budget End
2011-08-31
Support Year
25
Fiscal Year
2010
Total Cost
$559,322
Indirect Cost
Name
University of South Florida
Department
Physiology
Type
Schools of Medicine
DUNS #
069687242
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
Ott, Mackenzie M; Nuding, Sarah C; Segers, Lauren S et al. (2012) Central chemoreceptor modulation of breathing via multipath tuning in medullary ventrolateral respiratory column circuits. J Neurophysiol 107:603-17
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
Lindsey, Bruce G; Rybak, Ilya A; Smith, Jeffrey C (2012) Computational models and emergent properties of respiratory neural networks. Compr Physiol 2:1619-70
Ott, Mackenzie M; Nuding, Sarah C; Segers, Lauren S et al. (2011) Ventrolateral medullary functional connectivity and the respiratory and central chemoreceptor-evoked modulation of retrotrapezoid-parafacial neurons. J Neurophysiol 105:2960-75
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
Nuding, Sarah C; Segers, Lauren S; Shannon, Roger et al. (2009) Central and peripheral chemoreceptors evoke distinct responses in simultaneously recorded neurons of the raphé-pontomedullary respiratory network. Philos Trans R Soc Lond B Biol Sci 364:2501-16
Nuding, Sarah C; Segers, Lauren S; Baekey, David M et al. (2009) Pontine-ventral respiratory column interactions through raphe circuits detected using multi-array spike train recordings. J Neurophysiol 101:2943-60
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
Rybak, I A; O'Connor, R; Ross, A et al. (2008) Reconfiguration of the pontomedullary respiratory network: a computational modeling study with coordinated in vivo experiments. J Neurophysiol 100:1770-99

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