Chronic exposure in a low oxygen environment (i.e., chronic hypoxia, CH) elicits multiple physiological adjustments which improve O2 uptake and utilization. Amongst the most important of these is progressive increase in breathing which occurs over a period of 4-5 days in rats, and 7-10 days in humans. This ventilatory acclimatization to hypoxia (VAH) occurs as a consequence of functional changes in the oxygen-sensitive in the oxygen-sensitive chemoreflex pathway, which is comprised of multiple cellular components, including the primary chemoafferent neurons of the petrosal ganglion (PG). Although primary sensory neurons have traditionally been regarded as static relay connectors between their sensory receptors and the CNS, recent studies have demonstrated functionally significant phenotypic changes, including altered expression of neuropeptides and membrane receptor subtypes, in sensory neurons of dorsal root ganglia exposed to chronic stress and/or pathophysiological conditions. We have found that primary chemoafferent neurons in the rat PG, which innervate the arterial chemoreceptor type I cells of the carotid body, undergo adaptive changes during chronic exposure to a low-02 environment. These changes appear to be specific for chemoafferent neurons, and moreover, to result in significant functional adjustments at the level of chemotransmission in the carotid body. Our research program will undertake three specific aims: (I), assess the altered gene expression and phenotypic changes observed in PG neurons following exposure to CH; (II), investigate the factors/mechanisms which determine/control these neuroplastic changes in PG neurons; and (III), examine the relationship between altered phenotypic expression in chemoafferent neurons and changes in chemotransmission and chemosensitivity of the carotid body. The results from our experiments are expected to further elucidate the involvement of the carotid chemoreflex pathway, and in particular the chemoafferent neurons, in physiological adaptation to chronic chemostimulation.
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