The fundamental goal of this project is to understand mechanisms whereby early life experiences profoundly influence mechanisms of ventilatory control in adult mammals (i.e. developmental plasticity). In the first three years of this project, it was demonstrated that the ventilatory control system is subject to developmental plasticity in the hypoxic ventilatory response. Specifically, one month of perinatal hyperoxia (60 percent) causes a persistent attenuation of the hypoxic ventilatory response in adult rats, two to four months after the hyperoxic exposure had ended. Since similar effects are not observed in rats exposed to the same duration and level of hyperoxia as adults, this functional impairment is unique to development.
The aims of this proposal for competitive renewal are to extend these observations by testing the following hypotheses: 1) that perinatal hyperoxia causes persistent functional impairment of the hypoxic ventilatory response only within a limited developmental """"""""window,"""""""" approximately two weeks in length; 2) that slow, partial functional recovery occurs spontaneously with advancing age; and 3) that functional recovery of the hypoxic ventilatory response can be induced by sustained exposure to hypoxia, either within the developmental window or after the developmental window has expired. Experiments will combine neurophysiological recordings of hypoxic phrenic and carotid chemoafferent responses in anesthetized rats with measurements of the hypoxic ventilatory response in awake rats. These studies may have important clinical implications for infants subjected to oxygen therapy during critical care; they may suffer impaired chemoreflexes throughout their lives if excessive arterial oxygenation occurs during the developmental window. Further understanding of mechanism(s) that underlie developmental plasticity with its associated functional impairments may provide the rationale for therapeutic intervention, thereby enhancing 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 |
| Mitchell, Gordon S; Johnson, Stephen M (2003) Neuroplasticity in respiratory motor control. J Appl Physiol 94:358-74 |
| 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 |
| 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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