线粒体不仅产生ATP为细胞供能，线粒体可缓冲细胞内Ca2+，是Ca2+生物感应器，对神经元突触可塑性调控尤为重要，但目前不清楚线粒体是否参与呼吸可塑性调控？AIH诱导呼吸长时程易化(LTF)，dAIH已用于高位脊髓损伤呼吸衰竭病人的治疗。CIH诱导阻塞性睡眠呼吸暂停(OSA)实验模型。我们近期发现了呼吸中枢pre-BötC突触后树突线粒体参与dAIH诱导呼吸可塑性的形态学证据，亟需深入的机制研究。本项目拟采用整体动物和离体脑片实验，通过dAIH→LTF(生理)和CIH→OSA(病理)干预，结合形态学、电生理学、分子生物学、药理学等技术，探讨pre-BötC神经元突触后树突线粒体的结构-功能变化、CO活性以及突触联系，明确Ca2+－CaMKII、Ca2+－Miro1信号分子的关键作用，揭示线粒体参与pre-BötC呼吸可塑性调控机制，为OSA睡眠呼吸紊乱疾病提供实验依据和潜在的治疗对策。

Mitochondria not only generate ATP for cell energy supply, but also participate in Ca2+ buffering homeostasis, being Ca2+ biosensor, which is especially critical for neural synaptic plasticity. However, it is unknown whether mitochondria contribute to respiratory plasticity？Acute intermittent hypoxia (AIH) induces respiratory long-term facilitation (LTF). A d(daily)AIH paradigm has been used to treat patients with high-level spinal cord injury and respiratory failure. Chronic intermittent hypoxia (CIH), a serious pathological hypoxic paradigm, is applied as an animal model of obstructive sleep apnea (OSA). Our recent findings provide morphological evidence of postsynaptic dendritic mitochondria in contribution to respiratory plasticity in the pre-Bötzinger complex (pre-BötC) in aninals preconditioned with dAIH. Further studies are necessary to explore mitochondrial functions and their underling mechanisms. Combined with morphological, electrophysiological, molecular biological and pharmacological techniques, this project was aimed to investigate alterations of postsynaptic dendritic mitochondria in structure and function, cytochrome oxidase (CO) activity, and synaptic relationships in the pre-BötC in entire animals and isolated brainstem slices pretreated with dAIH→LTF (physiological) and CIH→OSA (pathological) challenges. We wish to clarify Ca2+－CaMKII and Ca2+－Miro1 signaling mechanisms underlying mitochondrion-mediated respiratory plasticity in the pre-BötC. This study will provide experimental evidence and potential therapeutic strategies for OSA and relative sleep respiratory disorders.