Learning to breathe: control of the inspiratory-expiratory phase transition shifts from sensory-to central-dominated during postnatal development in rats
Learning to breathe: control of the inspiratory-expiratory phase transition shifts from sensory-to central-dominated during postnatal development in rats
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DOI：
10.1113/jphysiol.2009.174599
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发表时间：
2009-10-15
影响因子：
5.5
通讯作者：
Dick, Thomas E.
中科院分区：
文献类型：
--
作者：
Dutschmann, Mathias;Moerschel, Michael;Dick, Thomas E.
吸气和呼气之间过渡动态调节的标志是吸气关闭开关 (IOS) 机制的定时。 IOS 由肺迷走神经传入反馈（Breuer-Hering 反射）和涉及 Kolliker-Fuse 核 (KFn) 的中枢相互作用介导。我们假设这两种控制 IOS 的机制之间的平衡可能在出生后发育过程中发生变化。我们使用不同出生后年龄的大鼠的原位灌注脑干制剂，通过比较对重复节律性迷走神经刺激的神经反应来测试这一假设，刺激频率与基线呼吸步调一致。在年龄 < P15（P，出生后天）时，膈神经活动（PNA）立即起搏并夹带至传入输入，并且这种模式在重复刺激下保持不变，表明迷走神经输入通常主导 IOS 的控制。相反，> P15 时的 PNA 夹带最初是微不足道的，但在重复迷走神经刺激或肺膨胀后增加。 PNA 对感觉输入模式的逐渐适应伴随着刺激序列之前预期中枢介导的 IOS 的出现。通过将 NMDA 受体拮抗剂双侧显微注射到 KFn 中来阻断预期的 IOS，并且 PNA 立即起搏和夹带，正如在年龄 < P15 时所看到的那样。我们的结论是，随着出生后成熟的进展，在使用重复刺激试验“训练”后，涉及 KFn 中 NMDA 受体的突触机制可以覆盖迷走神经诱发的 IOS。预期 IOS 可能意味着在介导 IOS 的会聚感觉和中枢突触通路中迄今为止未描述的模式学习和回忆形式。
The hallmark of the dynamic regulation of the transitions between inspiration and expiration is the timing of the inspiratory off-switch (IOS) mechanisms. IOS is mediated by pulmonary vagal afferent feedback (Breuer-Hering reflex) and by central interactions involving the Kolliker-Fuse nuclei (KFn). We hypothesized that the balance between these two mechanisms controlling IOS may change during postnatal development. We tested this hypothesis by comparing neural responses to repetitive rhythmic vagal stimulation, at a stimulation frequency that paces baseline breathing, using in situ perfused brainstem preparations of rats at different postnatal ages. At ages < P15 (P, postnatal days), phrenic nerve activity (PNA) was immediately paced and entrained to the afferent input and this pattern remained unchanged by repetitive stimulations, indicating that vagal input stereotypically dominated the control of IOS. In contrast, PNA entrainment at >P15 was initially insignificant, but increased after repetitive vagal stimulation or lung inflation. This progressive adaption of PNA to the pattern of the sensory input was accompanied by the emergence of anticipatory centrally mediated IOS preceding the stimulus trains. The anticipatory IOS was blocked by bilateral microinjections of NMDA receptor antagonists into the KFn and PNA was immediately paced and entrained, as it was seen at ages < P15. We conclude that as postnatal maturation advances, synaptic mechanisms involving NMDA receptors in the KFn can override the vagally evoked IOS after 'training' using repetitive stimulation trials. The anticipatory IOS may imply a hitherto undescribed form of pattern learning and recall in convergent sensory and central synaptic pathways that mediate IOS.