| Exposure to hypoxia, a decrease in oxygen levels, evokes a compensatory response. Acute hypoxia triggers a distinct pattern of respiratory and sympathetic motor activity during and after hypoxia. The evoked motor response results from integration of peripheral and central chemo-sensitive afferent inputs by the sympatho-respiratory neural network in the brainstem. Although several neurotransmitter systems and neuronal populations are involved in mediating the hypoxic response, the circuitry is unclear. Previous studies demonstrated that release of gamma-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the central nervous system, depresses respiratory activity during hypoxia. In addition, neuronal populations in the pons, a portion of the brainstem, mediate a decrease in respiratory frequency during and after hypoxia. Thus, we hypothesized that GABAA receptors in the pons participate in the hypoxic response.; To explore the role of the GABAA receptor in the acute hypoxic response, the receptor antagonist bicuculline was microinjected into regions involved in sympatho-respiratory neural control in the ventrolateral (vl) pons. This intervention altered only one component of the hypoxic response, the hypoxic ventilatory decline (HVD). Additional studies demonstrated that the acute hypoxic response was blunted by conditioning rats for 14 d to chronic hypobaric hypoxia (CHH), a model of living at high altitude. In addition, long-term facilitation (LTF), a persistent increase in the sympatho-respiratory activity after repeated hypoxic challenges, was attenuated.; The expression of LTF is mediated in part by neuronal populations in the pons. Our results revealed that GABAA receptor subunit expression in the pons changes along with the CHH-induced physiologic changes. Upregulation of the GABAA receptor alpha4 subunit mRNA expression occurred after 7 d CHH. Furthermore, de novo expression of delta and alpha6, normally found exclusively in the cerebellum, was observed after 14 d. Binding assays confirmed the increase in receptors and immunohistochemistry verified that CHH-induced GABAA receptor subunit expression was localized in sympatho-respiratory areas within the pons. Together, our findings suggest that GABAA receptor expression in the pons participates in the physiologic response and adaptation of the sympatho-respiratory system to hypoxia. |
