Neural mechanisms mediating respiratory neuroplasticity

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Breathing is relentless.  It begins in-utero, is continuous at birth and rarely fails.  The brain region that induces breathing is exquisitely sensitive to challenges affecting carbon dioxide and oxygen levels.  It also exhibits considerable flexibility (plasticity) so that respiratory needs are maintained in the face of environmental and physiological changes.  This grant proposal examines the fundamental physiological processes underlying an important form of respiratory plasticity called long-term facilitation (LTF).  Respiratory LTF is a persistent increase in breathing that lasts for hours after exposure to several brief episodes of low oxygen levels.  LTF is only manifested when a brain chemical called serotonin is released.  However, the brain region that releases serotonin to induce LTF is unknown.  Moreover, this important respiratory behaviour has never been studied during early development.  Accordingly, the major goal of this research is to understand how the central serotonin system is turned-on to initiate LTF in the developing respiratory system. This proposal's working hypothesis is that the serotonergic raphe nucleus plays a central role in the induction of LTF and that this respiratory behaviour is present in newborn animals.   This research is significant because it explores the fundamental brain mechanisms that mediate a form of respiratory plasticity called LTF.  This is biologically important because this mechanism may help certain animals cope with stressful environmental changes.  This is also clinically relevant because LTF may be an adaptive respiratory behaviour that occurs in disease states involving intermittent exposures to hypoxia such as sudden infant death syndrome and obstructive sleep apnea.