Sensory deprivation in critical early periods of development irreversibly impairs central nervous system function (eg. visual and auditory systems). The objective of this project is to determine if sensory guidance is necessary for the normal development of ventilatory control. Specifically, our goal is to determine if early sensory feedback from peripheral arterial chemoreceptors is essential for the development of a normal hypoxic ventilatory response. Newborn rats are exposed to moderate hyperoxia within the first month of life, thereby suppressing feedback from peripheral chemoreceptors while voiding hyperoxic toxicity. Preliminary results indicate that their hypoxic ventilatory response is severely impaired several months after normal oxygen conditions had been restored. Experiments are proposed to extend these exciting observations, and to determine if the functional impairment results from changes in the central nervous system, carotid chemoreceptors, or both. These objectives will be pursued by combining measurements of the hypoxic ventilatory response in awake rats with neurophysiological techniques in anesthetized rats to determine the site(s) of functional impairment.
The specific aims are to test four hypotheses: 1) suppression of peripheral chemoreceptor inputs by perinatal hyperoxia irreversibly impairs the hypoxic ventilatory response; 2) suppression of peripheral chemoreceptor inputs via perinatal hyperoxia impairs central integration of carotid chemoreceptor inputs; 3) perinatal hyperoxia directly impairs carotid chemoreceptor function; and/or 4) perinatal hyperoxia prevents maturation of mechanisms that cause central hypoxic depression in the newborn, thereby diminishing the hypoxic ventilatory response. These experiments imply that normal ventilatory control mechanisms are susceptible to developmental plasticity, contrary to conventional thinking. This finding may have important clinical relevance to infants subjected to oxygen therapy during critical care; they may suffer from impaired chemoreceptor reflexes throughout their lives. A thorough understanding of mechanism(s) that underlie developmental plasticity and functional impairment may provide the rationale for therapeutic intervention, restoring plasticity and allowing functional recovery.
| Babb, Tony G; Wood, Helen E; Mitchell, Gordon S (2010) Short- and long-term modulation of the exercise ventilatory response. Med Sci Sports Exerc 42:1681-7 |
| Bavis, Ryan W; Johnson, Rebecca A; Ording, Kari M et al. (2006) Respiratory plasticity after perinatal hypercapnia in rats. Respir Physiol Neurobiol 153:78-91 |
| Bavis, R W; Olson Jr, E B; Vidruk, E H et al. (2004) Developmental plasticity of the hypoxic ventilatory response in rats induced by neonatal hypoxia. J Physiol 557:645-60 |
| Feldman, Jack L; Mitchell, Gordon S; Nattie, Eugene E (2003) Breathing: rhythmicity, plasticity, chemosensitivity. Annu Rev Neurosci 26:239-66 |
| Bavis, Ryan W; Mitchell, Gordon S (2003) Intermittent hypoxia induces phrenic long-term facilitation in carotid-denervated rats. J Appl Physiol 94:399-409 |
| Bavis, R W; Olson Jr, E B; Vidruk, E H et al. (2003) Level and duration of developmental hyperoxia influence impairment of hypoxic phrenic responses in rats. J Appl Physiol 95:1550-9 |
| Zabka, A G; Mitchell, G S; Olson Jr, E B et al. (2003) Selected contribution: chronic intermittent hypoxia enhances respiratory long-term facilitation in geriatric female rats. J Appl Physiol 95:2614-23; discussion 2604 |
| Behan, Mary; Zabka, Andrea G; Thomas, Cathy F et al. (2003) Sex steroid hormones and the neural control of breathing. Respir Physiol Neurobiol 136:249-63 |
| Mitchell, Gordon S; Johnson, Stephen M (2003) Neuroplasticity in respiratory motor control. J Appl Physiol 94:358-74 |
| Johnson, Stephen M; Wilkerson, Julia E R; Wenninger, Michael R et al. (2002) Role of synaptic inhibition in turtle respiratory rhythm generation. J Physiol 544:253-65 |
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