The objective of the project is to determine if intermittent hypoxia induces neural plasticity in the ventilatory control system. Specifically, the goal is to determine if repeated activation of the hypoxic ventilatory control system by chronic intermittent hypoxia (CIH) induces a persistent functional enhancement of the system. Adult male rats will be exposed to CIH (11 percent 02/air: 5-min/5-min, 12 h/day, 7 consecutive nights). Preliminary results indicate a persistent and profound functional enhancement of the system, observed in three time- dependent mechanisms in phrenic and hypoglossal neural output: 1) enhancement of short term hypoxic response; 2) elimination of post- hypoxia frequency decline (a decrease in phrenic burst frequency that lasts minutes after isocapnic hypoxia), and 3) augmentation of long-term facilitation (a serotonin dependent enhancement of respiratory activity that lasts for many minutes to hours after episodes of isocapnic hypoxia). These investigators plan to extend their observations to determine if the functional enhancement is of central and/or peripheral origin, and to investigate the involvement of neurochemical serotonin in the underlying mechanisms. These objectives will be pursued by combining plethysmographic measurements of the hypoxic ventilatory response in awake rats with neurophysiological experiments in anesthetized rats. Four specific hypotheses will be tested: 1) CIH causes prolonged enhancement of acute and time dependent hypoxic ventilatory responses; 2) CIH enhances central integration of carotid chemoafferent inputs; 3) CIH enhances carotid chemosensory transduction; and 4) functional enhancement of the system following CIH requires serotonergic mechanisms. These experiments imply that a fully developed, hypoxic ventilatory control system still exhibits an impressive degree of plasticity. The information derived from the proposed studies may contribute an understanding to neural plasticity in ventilatory control and may provide the rationale for its therapies to some diseases.
