先天性中枢性低通气综合征（CCHS）是一种严重的呼吸自主控制障碍综合征，其病因可能与Phox2b基因突变所致呼吸中枢化学感受器的原发性缺陷有关，因此探讨中枢化学感受器Phox2b神经元调控呼吸运动的机制具有重要的临床意义。Phox2b表达在包括孤束核在内的呼吸反射传入通路上，且研究表明Phox2b神经元通过其化学敏感性反应参与呼吸反射，但这类神经元在孤束核是否参与呼吸调控以及化学敏感性反应的机制还未见报道。为回答这些问题，本研究首先观察选择性刺激Phox2b-eGFP-Jx99转基因小鼠孤束核Phox2b神经元是否驱动呼吸运动；其次观察离体条件下Phox2b神经元的化学敏感性反应特征以及这类细胞的生物化学表型；最后观察Task-2和/或Kv12.1电流是否为Phox2b神经元化学敏感性的离子基础。研究结果将为CCHS及呼吸调控异常性疾病提供新的病因线索以及分子和基因水平的治疗思路。

Congenital central hypoventilation syndrome (CCHS) is a disorder characterized by the absence of adequate autonomic control of respiration and the main cause is closely related to Phox2b gene mutation leading to idiopathic deficiency of central respiratory chemoreceptors. Therefore unveiling the mechanism underlying respiratory control by Phox2b-expressing neurons of central chemoreceptors will definitely contribute to clinical significance. Phox2b is expressed afferent pathway of respiratory reflex circuits including NTS and Phox2b-expressing neurons are thought to regulate breathing through chemosensitive responses, however it remains unanswered whether the NTS Phox2b-expressing neurons are involved in respiratory control and what mechanism underpins neuronal chemosensitivity. To address these issues, this project seeks to test whether photostimulation of Phox2b-expressing neurons of the NTS in Phox2b-eGFP-Jx99 mice can affect respiratory drive, to test characterization of Phox2b-expressing neurons' chemosensitivity and their biochemical phenotype, to test if Task-2 and/or Kv12.1 currents are the basis for chemosensitivity of NTS Phox2b-expressing neurons. The results to be obtained will be expected to demonstrate reliable and valuable evidence contributing to providing novel pathogenic clues of CCHS and molecular and genetic therapy strategies.