下丘脑-背侧蓝斑底核orexin通路调控REM睡眠的机制研究

The hypothalamic orexinergic system plays an important role in promoting wakefulness and also in inhibiting rapid eye movement(REM) sleep. Recent studies have shown that the orexinergic fibers are distributed within the dorsal subcoeruleus nucleus(SubCD), which is tightly related to the initiation and maintenance of REM sleep. However, little is konwn about the role of orexin in these areas. In this project, we will first investigate the effect of orexin on the neuronal activity of SubCD neurons and identify the underlying receptor and ionic mechanisms. Then we will observe the relationship of neuronal activity betweem the hypothalamic orexin neurons and the GABAergic and glutamatergic neurons of SubCD in vivo. Also, we will explore how this pathway influence REM sleep in sleep-wake cycles. Multiple recordings including in vivo mult-channel recordings, EEG/EMG recordings and whole-cell clamp patch recordings will be used frequently in our project, as well as other methods such as optogenetic technology, histochemical stainning and behavioral test. Our hypothesis is that orexin may inhibit REM sleep through acting on the GABAergic neurons located within the SubCD. We expect to clarify the role of this pathway in the control of REM sleep and also the underlying mechanisms which will benefit for the better understanding of the role of central orexinergic system in the sleep and wakefulness control.

下丘脑orexin系统是中枢重要的促觉醒系统，且对REM睡眠有着重要的抑制性调节作用。近期的研究表明orexin纤维直接投射至与REM睡眠调节密切相关的背侧蓝斑底核，然而其作用机制尚不明确。因此，本研究拟采用形态学、脑片膜片钳、在体电生理、多导睡眠记录、光遗传学等技术，首先阐明orexin调节背侧蓝斑底核神经元活动的突触和分子信号机制。在此基础上，进一步在体观察下丘脑orexin神经元活动对该脑区不同GABA能和谷氨酸能神经元放电特征的影响，进而阐明该通路在REM睡眠中的调节作用原理，以期为深入理解睡眠觉醒周期的机制以及相关疾病的干预提供新思路。