VTA区不同亚型GABA能神经元在术后睡眠障碍中的神经环路调控机制

术后睡眠障碍（PSD）是麻醉后严重并发症。申请者发表Nat Neurosci论著证实中脑腹侧被盖区（VTA）Glu和GABA能神经元对觉醒及NREM睡眠有调控作用。深入研究发现VTA区GABA能神经元在促NREM睡眠时表现为三种突触后电流，提示其存在不同亚型。本课题拟用多种模式动物，使用光遗传、化学遗传、在体电生理、钙成像、脑深部核团显微观察等技术，证明VTA区GABA能神经元存在两大类，一类为促进NREM睡眠的神经元（VIP、SOM），在NREM睡眠时活性升高，长投射作用于下丘脑Orexin能神经元；另一类为抑制促觉醒核团的神经元（PV、GaD2），短投射作用于VTA区的多巴胺及谷氨酸能神经元，维持NREM睡眠。最终证实麻醉后第二类神经元被抑制，睡眠稳态被破坏从而引发了PSD这一假说，并阐明VTA区GABA能神经元亚型在睡眠调节和PSD发生中的环路调控机制，为PSD防治提供新的靶点。

The number of global operations is increasing year by year, and the occurrence of postoperative sleep disorders is also increasing.The ventral tegmental area (VTA) of the midbrain is an important nuclear group that regulates sleep and wakefulness, and its GABAergic neurons play a strong role in promoting NREM sleep but its specific mechanism is still unclear.The applicant's previous research showed that when GABAergic neurons in the VTA promoted NREM sleep, the discharge pattern showed three types of post-synaptic currents, suggesting that there are different subtypes of GABAergic neurons in the VTA. Based on the earlier study, the applicant found that there are subtypes of GABAergic neurons such as PV, SOM, VIP, and GAD2 in the VTA . There are obvious differences in the regulation of these types of neurons when they play the role of promoting NREM sleep by DREADDs. This subject intends to use a variety of model animals, using optogenetics, chemical inheritance, in vivo electrophysiology, calcium imaging, microscopic observation of deep brain nuclei to prove that there are two types of GABAergic neurons in the VTA. One type (VIP, SOM neurons) to directly promote NREM sleep, and the other (PV, GAD2 neurons) for the inhibition of wake-promoting neurons and thus indirectly play a role in contributing NREM sleep, while resulting in circadian rhythm changes to Maintain the balance of sleep. The general anesthesia drugs inhibited PV and GAD2 neurons and then caused postoperative sleep disorders. This study provides a theoretical basis of solving daily sleep disorders and postoperative sleep disorders caused by anesthetic drugs.