Postnatal Intermittent Hypoxia and Respiration: Potenti*

描述（由申请人提供）：间歇性缺氧（IH）是临床医学中的常见病症（例如，睡眠呼吸暂停，SIDS），其具有相当高的发病率和死亡率。此外，生物适应IH表明形成特定形式的神经元可塑性。虽然大量的研究IH的影响已经在成熟的哺乳动物，很少，如果有任何工作已经做了在出生后的发展，一个独特的时期，神经元的脆弱性和适应的早期阶段。因此，我们假设，出生后间歇性缺氧，如发生在睡眠呼吸暂停，可能会施加长期的修改呼吸控制，从而导致一种形式的亚可塑性的呼吸模式。出生后早期IH诱导的呼吸网络的后一种修改可以施加呼吸反应系统的功能有利或适应不良的改变。为了研究这个问题，我们将：（i）描述出生后IH对正常氧通气和对自由行为大鼠的低氧和高二氧化碳呼吸反应的影响。(ii)评估IH对膈运动神经长时程易化（LTF）的影响。(iii)确定信号通路的潜在作用，特别是蛋白激酶C（PKC），在通过发展的IH施加的通气的长期修改。因此，这项工作将有助于了解潜在的机制介导不仅早期适应IH，但也提供了见解通气，可能会发展时，条件刺激在成熟的关键阶段应用的持久变化。

DESCRIPTION (provided by applicant): Intermittent hypoxia (IH) is a frequent condition in clinical medicine (e.g., sleep apnea, SIDS), which bears substantial morbidity and mortality. Furthermore, organismal adaptations to IH suggest the formation of specific forms of neuronal plasticity. While substantial study of the effects of IH has been performed in the mature mammal, little if any work has been done during the early phases of post-natal development, a unique period of neuronal vulnerability and adaptation. Therefore, we hypothesized that post-natal intermittent hypoxia, such as occurs in sleep apnea, may impose long-term modifications in respiratory control, thereby leading to a form of metaplasticity of respiratory patterning. The latter modification of the respiratory network induced by early post-natal IH could impose either a functionally favorable or a maladaptive alteration of the respiratory response system. To examine this issue, we will: (i) characterize the effects of post-natal IH on normoxic ventilation and on hypoxic and hypercapnic ventilatory responses in freely behaving rats.; (ii) assess the effects of IH on phrenic motor nerve long-term facilitation (LTF).; (iii) determine the potential role of signaling pathways, particularly protein kinase C (PKC), in the long-term modification of ventilation imposed by IH through development. This work will therefore contribute to the understanding of potential mechanisms mediating not only early adaptations to IH but also provide insights to long-lasting changes in ventilation that may develop when a conditioning stimulus is applied during critical phase of maturation.