It is the purpose of this 5-year program to investigate molecular mechanisms involved in arterial chemoreception during postnatal development. In particular, the hypothesis that the net result of neurotransmission in arterial chemoreceptors is inhibitory and, as such, produces unstable ventilation will be tested. It is further proposed that the lack of the induction of immediate-early genes in cells of the chemoreceptor neural pathway (i.e., carotid bodies, petrosal ganglia, NTS and hypoglossal) by excitatory stimuli will serve as a marker of this inhibition. The applicant will use in situ hybridization histochemistry: a) to characterize the distribution of neurotransmitters and their receptors in cells of the carotid bodies and petrosal ganglia; b) to determine the effect of development on the induction of the immediate-early gene in cells of the chemoreceptor neural pathways; and c) to determine the effects of acute and chronic receptor agonists and antagonists on gene expression in response to peripheral and central chemoreceptor activation (via hypoxia).
