舌下神经长时程易化(LTF)与阻塞性睡眠呼吸暂停综合征(OSAS)的治疗密切相关。5-羟色胺(5-HT)和去甲肾上腺素(NE)能神经纤维参与LTF表达，但其细胞内信号机制不清楚。我们预实验首先发现舌下神经核内5-HT主导兴奋性突触传递，而NE表现兴奋-抑制双重突触传递特征，我们提出了LTF表达的5-HT/NE(突触前)→ 5-HT2AR/α1-AdR(胞膜)→ CaMKII/PKC(突触后)→ CREB(胞核)机制。本项目拟以慢性间断性缺氧（CIH）、LTF大鼠模型为实验平台，以脑干呼吸网络(包括pre-B?tzinger complex、舌下神经核、疑核)为研究对象，以上述通路为研究核心，结合免疫组化、免疫电镜、电生理、分子生物学等技术，探讨舌下神经LTF表达的突触可塑性机制，明确5-HT、NE能神经纤维在其中的不同功能意义，为OSAS等睡眠呼吸紊乱疾病提供实验依据和治疗对策。

Hypoglossal long-term facilitation (LTF) is thought to be in close relationship with treatment for obstructive sleep apnea syndrome (OSAS). Serotonergic (5-HT) and norepinephrinergic (NE) nerve fibers have been demonstrated to be attributed to LTF expression. However,their intracellular signaling mechanisms underlying LTF formation are largely unknown so far. Our pilot studys first identified different synaptic characteristics between 5-HT and NE innervation that 5-HT made excitatory synapses and NE formed excitatory-inhibitory dual synaptic transmissions onto neurons in the hypoglossal nucleus in rats. We hypothesized a pathway of 5-HT/NE (presynaptic) → 5-HT2AR/α1-AdR (cell membrane) → CaMKII/PKC (postsynaptic) → CREB (nucleus) that would contribute to LTF expression. Using immunohistochemical, immunoelectron microscopic, electrophysiological, and molecular biological approaches, we aimed to investigate mechanisms of synaptic plasticity in mediation of LTF expression in brainstem respiratory network, including the pre-B?tzinger complex,the hypoglossal nucleus, and the ambiguus nucleus,in OSAS and LTF rat models. We wish to unravel different functional roles of 5-HT and NE nerve system in attribution to LTF expression. The present study will provide experimental evidence and treatmental strategies for OSAS sleep disorder diseases.