睡眠呼吸障碍是一组以睡眠中呼吸异常为主要表现的疾病，呼吸化学感受器和呼吸中枢模式发生器的功能异常可能是此类疾病的重要发生机制。我们发现，孤束核存在中枢呼吸化学感受器神经元，激活表达配对同源盒基因（Phox2b）的孤束核神经元可增加基础肺通气，损毁此类神经元减弱高碳酸性通气反应，然而此类神经元是否通过兴奋中枢模式发生器中的前包钦格复合体（preBötC）发挥作用尚未研究。因此，本项目拟揭示支配preBötC的孤束核Phox2b神经元参与呼吸调控的环路机制。我们将观察支配preBötC的孤束核Phox2b神经元对呼吸的调控作用；揭示孤束核Phox2b神经元与preBötC神经元之间突触传递的分子机制；分析孤束核Phox2b神经元的生物化学表型；探讨臂旁核神经元是否参与孤束核Phox2b神经元调控呼吸的作用。研究结果将为揭示睡眠呼吸障碍疾病的发病机制提供实验依据。

Sleep-disordered breathing is characterized by abnormal breathing during sleep. One of the most important mechanisms responsible for sleep-disordered breathing is most likely ascribed to dysfunction of respiratory chemoreceptors and/or respiratory central pattern generator. Our recent studies demonstrate that selective activation of paired-homeobox gene 2b (Phox2b)-containing neurons vigorously increased basal pulmonary ventilation in the nucleus tractus solitarius (NTS); selective ablation of these neurons impaired a hypercapnic ventilatory response. However, it remains poor understood whether such above effects are ascribed to downstream activation of preBötzinger complex (preBötC) neurons by Phox2b-expressing NTS neurons. Therefore, the aim of this project is to underpin the mechanism responsible for control of breathing by Phox2b-expressing neurons projecting to the preBötC. To that end, we will seek to determine whether activation of the Phox2b-expressing neurons projecting to the preBötC reinforces breathing, to reveal the molecular mechanism of synaptic transmissions between the Phox2b-expressing neurons and preBötC neurons, to analyze biochemical phenotypes of Phox2b-expressing neurons, and finally to assess whether the parabrachial nucleus neurons contribute to respiratory roles of Phox2b-expressing neurons. These results will provide experimental evidence for better understanding the pathogenic mechanism of sleep-disordered breathing.