Striatal adenosine A(2A) receptor neurons control active-period sleep via parvalbumin neurons in external globus pallidus.
Striatal adenosine A(2A) receptor neurons control active-period sleep via parvalbumin neurons in external globus pallidus.
复制标题
纹状体腺苷 A(2A) 受体神经元通过外部苍白球中的小清蛋白神经元控制活动期睡眠
DOI：
10.7554/elife.29055
复制
发表时间：
2017-10-12
期刊：
影响因子：
7.7
通讯作者：
Huang ZL
中科院分区：
文献类型：
--
作者：
Yuan XS;Wang L;Dong H;Qu WM;Yang SR;Cherasse Y;Lazarus M;Schiffmann SN;d'Exaerde AK;Li RX;Huang ZL
纹状体功能障碍经常与睡眠障碍有关。然而，尽管纹状体密集表达腺苷A2 A受体（A2 ARs），但其在睡眠-觉醒调节中的作用却很少受到关注。在这里，我们发现，在纹状体的特定亚区的A2 AR神经元的化学发生激活诱导非快速眼动（NREM）睡眠显着增加。解剖映射和免疫电镜显示，纹状体A2 AR神经元支配的外部苍白球（GPe）的地形组织的方式，并优先形成抑制性突触与GPe小清蛋白（PV）神经元。此外，GPe PV神经元的损伤取消了纹状体A2 AR神经元的睡眠促进作用。此外，化学发生抑制纹状体A2 AR神经元导致小鼠活跃期NREM睡眠显著减少，而非活跃期NREM睡眠不明显。这些发现揭示了纹状体A2 AR神经元/GPe PV神经元回路在睡眠控制中的突出贡献。
Dysfunction of the striatum is frequently associated with sleep disturbances. However, its role in sleep-wake regulation has been paid little attention even though the striatum densely expresses adenosine A2A receptors (A2ARs), which are essential for adenosine-induced sleep. Here we showed that chemogenetic activation of A2AR neurons in specific subregions of the striatum induced a remarkable increase in non-rapid eye movement (NREM) sleep. Anatomical mapping and immunoelectron microscopy revealed that striatal A2AR neurons innervated the external globus pallidus (GPe) in a topographically organized manner and preferentially formed inhibitory synapses with GPe parvalbumin (PV) neurons. Moreover, lesions of GPe PV neurons abolished the sleep-promoting effect of striatal A2AR neurons. In addition, chemogenetic inhibition of striatal A2AR neurons led to a significant decrease of NREM sleep at active period, but not inactive period of mice. These findings reveal a prominent contribution of striatal A2AR neuron/GPe PV neuron circuit in sleep control.