Understanding the central nervous system mechanisms controlling breathing in mammals represents one of the fundamental challenges in contemporary respiratory physiology. Establishing neural mechanisms at the cellular and synaptic level remains a central problem in unraveling the nature and function of the respiratory control system. This proposal exploits the unique properties of in vitro preparations from the neonatal rat nervous system to study basic cellular and synaptic mechanisms. We have developed novel in vitro slice preparation of the neonatal rat brainstem that contain functionally active respiratory networks and provide unparalleled access to neuronal elements critical for generation and transmission of respiratory rhythm under conditions that are optimal for analysis of cellular and synaptic processes. We propose a set of closely interrelated projects whose specific aims are to determine: (1) basic neuronal substrates for generation and transmission of respiratory rhythm in the neonatal nervous system; (2) cellular and synaptic mechanisms of rhythm generation, (3) neurochemical and synaptic mechanisms for modulation of rhythm, and (4) dynamical properties of respiratory neurons and networks by computational methods. The long-range goal of this multidisciplinary set of projects is to explain the ontogeny and neurogenesis of respiratory rhythm and pattern in mammals in terms of the biophysical, synaptic and network properties of CNS respiratory neurons. Information to be obtained from this proposal is fundamental for understanding basic human physiology and pathologies where ventilatory failure results from dysfunction of CNS mechanisms controlling breathing, including such diseases as apnea of prematurity, congenital central hypoventilation, central alveolar hypoventilation, and 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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University of California Los Angeles
Schools of Medicine
Los Angeles
United States
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Dick, T E; Dutschmann, M; Feldman, J L et al. (2018) Facts and challenges in respiratory neurobiology. Respir Physiol Neurobiol 258:104-107
Shao, Xuesi M; López-Valdés, Héctor E; Liang, Jing et al. (2017) Inhaled nicotine equivalent to cigarette smoking disrupts systemic and uterine hemodynamics and induces cardiac arrhythmia in pregnant rats. Sci Rep 7:16974
Yackle, Kevin; Schwarz, Lindsay A; Kam, Kaiwen et al. (2017) Breathing control center neurons that promote arousal in mice. Science 355:1411-1415
Cui, Yan; Kam, Kaiwen; Sherman, David et al. (2016) Defining preBötzinger Complex Rhythm- and Pattern-Generating Neural Microcircuits In Vivo. Neuron 91:602-14
Li, Peng; Janczewski, Wiktor A; Yackle, Kevin et al. (2016) The peptidergic control circuit for sighing. Nature 530:293-297
Feldman, Jack L; Kam, Kaiwen (2015) Facing the challenge of mammalian neural microcircuits: taking a few breaths may help. J Physiol 593:3-23
Shao, Xuesi M; Xu, Bin; Liang, Jing et al. (2013) Nicotine delivery to rats via lung alveolar region-targeted aerosol technology produces blood pharmacokinetics resembling human smoking. Nicotine Tob Res 15:1248-58
Kam, Kaiwen; Worrell, Jason W; Ventalon, Cathie et al. (2013) Emergence of population bursts from simultaneous activation of small subsets of preBotzinger complex inspiratory neurons. J Neurosci 33:3332-8
Feldman, Jack L; Del Negro, Christopher A; Gray, Paul A (2013) Understanding the rhythm of breathing: so near, yet so far. Annu Rev Physiol 75:423-52
Kam, Kaiwen; Worrell, Jason W; Janczewski, Wiktor A et al. (2013) Distinct inspiratory rhythm and pattern generating mechanisms in the preBotzinger complex. J Neurosci 33:9235-45

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