Striatal neurons expressing dopamine D1 receptor promote wakefulness in mice
Striatal neurons expressing dopamine D1 receptor promote wakefulness in mice
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DOI：
10.1016/j.cub.2021.12.026
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发表时间：
2022-02-07
期刊：
影响因子：
9.2
通讯作者：
Huang, Zhi-Li
中科院分区：
文献类型：
--
作者：
Dong, Hui;Chen, Ze-Ka;Huang, Zhi-Li
帕金森病（PD）患者患有严重的睡眠障碍。基底神经节（BG）的病理生理学是PD的基础，背侧纹状体是BG的主要输入途径。然而，背侧纹状体在控制睡眠-觉醒周期中的作用和机制仍不清楚。为了证明背侧纹状体内多巴胺D1受体（D1 R）阳性神经元在促进觉醒中的贡献，我们将光遗传学操作和纤维光度法与D1 R-Cre小鼠的脑电图/肌电图记录相结合。结果，纹状体D1 R神经元的光遗传学激活诱导从非快速眼动（NREM）睡眠到觉醒的立即转变，而纹状体D1 R神经元的抑制通过化学遗传学减弱觉醒。多通道纤维光度记录显示，纹状体D1 R神经元的活动与BG上游，即前额叶皮层和内侧背丘脑同步，在NREM到唤醒过渡期间立即增加活动，并在唤醒到NREM过渡期间迅速下降。进一步的光遗传学操作揭示了纹状体D1 R神经元通过上游、皮质纹状体、丘脑纹状体和黑质纹状体投射以及通过下游、纹状体脚内或纹状体黑质途径控制觉醒的突出贡献。总之，我们的研究结果揭示了通过纹状体D1 R神经元调节觉醒的回路。纹状体D1 R神经元通过整合皮质纹状体、丘脑纹状体和黑质纹状体的投射和纹状体-脚内或纹状体黑质通路的神经支配在控制觉醒中起重要作用。
Patients with Parkinson's disease (PD) suffer from severe sleep disorders. Pathophysiology of the basal ganglia (BG) underlies PD, and the dorsal striatum represents the major input pathway of the BG. However, the roles and mechanisms of the dorsal striatum in controlling sleep-wake cycles remain unknown. To demonstrate the contribution of dopamine D1 receptor (D1R)-positive neurons within the dorsal striatum in promoting wakefulness, we combined optogenetic manipulations and fiber photometry with electroencephalography/electromyography recording in D1R-Cre mice. As a result, optogenetic activation of striatal D1R neurons induced immediate transitions from non-rapid eye movement (NREM) sleep to wakefulness, whereas inhibition of striatal D1R neurons attenuated wakefulness by chemogenetics. Multi-channel fiber photometry recordings revealed that the activity of striatal D1R neurons synchronized with that of BG upstreams, namely the prefrontal cortex and mediodorsal thalamus, in terms of immediate increase in activity during NREM-to-wake transitions and rapid decease during wake-to-NREM transitions. Further optogenetic manipulations revealed a prominent contribution of striatal D1R neurons in control of wakefulness by upstream, corticostriatal, thalamostriatal, and nigrostriatal projections and via downstream, striato-entopeduncular, or striatonigral pathways. Taken together, our findings revealed a circuit regulating wakefulness through striatal D1R neurons. Striatal D1R neurons play an important role in controlling wakefulness by integrating the corticostriatal, thalamostriatal, and nigrostriatal projections and innervation of striato-entopeduncular or striatonigral pathways.