Neural mechanisms mediating respiratory neuroplasticity

呼吸是无情的。它从子宫内开始，在出生时持续，很少失败。诱导呼吸的大脑区域对影响二氧化碳和氧气水平的挑战非常敏感。它还表现出相当大的灵活性（可塑性），以便在面对环境和生理变化时维持呼吸需求。这项拨款提案研究了一种重要的呼吸可塑性形式的基本生理过程，称为长期促进（LTF）。呼吸性慢性呼吸衰竭是在暴露于几次短暂的低氧发作后持续数小时的呼吸增加。LTF只有在一种叫做血清素的大脑化学物质被释放时才会表现出来。然而，释放血清素诱导LTF的大脑区域尚不清楚。此外，这种重要的呼吸行为在早期发育过程中从未被研究过。因此，本研究的主要目标是了解中枢血清素系统如何在发育中的呼吸系统中启动LTF。该建议的工作假设是，血清素能中脑核在LTF的诱导中起核心作用，并且这种呼吸行为存在于新生动物中。这项研究意义重大，因为它探索了调节一种称为LTF的呼吸可塑性形式的基本大脑机制。这在生物学上是很重要的，因为这种机制可以帮助某些动物应对紧张的环境变化。这也具有临床相关性，因为LTF可能是一种适应性呼吸行为，发生在间歇性暴露于缺氧的疾病状态中，如婴儿猝死综合征和阻塞性睡眠呼吸暂停。

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.