Astroglial Calcium Signaling Encodes Sleep Need in Drosophila.
Astroglial Calcium Signaling Encodes Sleep Need in Drosophila.
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DOI：
10.1016/j.cub.2020.10.012
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发表时间：
2021-01-11
期刊：
影响因子：
--
通讯作者：
Wu MN
中科院分区：
文献类型：
--
作者：
Blum ID;Keleş MF;Baz ES;Han E;Park K;Luu S;Issa H;Brown M;Ho MCW;Tabuchi M;Liu S;Wu MN
睡眠是在自我平衡的控制下，因此增加觉醒会产生睡眠需求并触发睡眠驱动。然而，对睡眠需求编码的分子和细胞途径知之甚少。此外，睡眠需求如何以及何时转化为睡眠驱动的机制尚不清楚。在这里，使用离体和体内成像，我们在果蝇中显示，星形胶质细胞Ca 2+信号随着睡眠需求的增加而增加。我们证明，这种信号是依赖于一个特定的L型钙离子通道，是必要的稳态睡眠反弹。星形胶质细胞中的热生成增加Ca 2+诱导持续的睡眠行为，我们利用这种表型进行睡眠的稳态调节所需的基因的遗传筛选。从这个大规模的屏幕上，我们确定TyrRII，睡眠稳态所需的星形胶质细胞的单胺能受体。TyrRII水平在睡眠剥夺后以Ca 2+依赖性方式升高，促进星形胶质细胞Ca 2+的进一步增加，并导致正反馈回路。此外，我们的研究结果表明，星形胶质细胞然后通过上调和释放白细胞介素-1类似物Spätzle将这种睡眠需求传递到睡眠驱动电路，然后作用于R5神经元上的Toll受体。这些发现定义了编码睡眠需求的星形胶质细胞Ca 2+信号传导机制，并揭示了睡眠稳态控制系统的动态特性。睡眠需求是如何被感知、整合并传达给下游睡眠回路的，人们对此知之甚少。Blum等人发现，果蝇星形胶质细胞中的Ca 2+瞬变与清醒时间相关，并确定了编码睡眠需求的这些信号的产生、放大和传输的分子和电路机制。
Sleep is under homeostatic control, whereby increasing wakefulness generates sleep need and triggers sleep drive. However, the molecular and cellular pathways by which sleep need is encoded are poorly understood. In addition, the mechanisms underlying both how and when sleep need is transformed to sleep drive are unknown. Here, using ex vivo and in vivo imaging, we show in Drosophila that astroglial Ca2+ signaling increases with sleep need. We demonstrate that this signaling is dependent on a specific L-type Ca2+ channel and is necessary for homeostatic sleep rebound. Thermogenetically increasing Ca2+ in astrocytes induces persistent sleep behavior, and we exploit this phenotype to conduct a genetic screen for genes required for the homeostatic regulation of sleep. From this large-scale screen, we identify TyrRII, a monoaminergic receptor required in astrocytes for sleep homeostasis. TyrRII levels rise following sleep deprivation in a Ca2+-dependent manner, promoting further increases in astrocytic Ca2+ and resulting in a positive-feedback loop. Moreover, our findings suggest that astrocytes then transmit this sleep need to a sleep drive circuit, by upregulating and releasing the interleukin-1 analog Spätzle, which then acts on Toll receptors on R5 neurons. These findings define astroglial Ca2+ signaling mechanisms encoding sleep need and reveal dynamic properties of the sleep homeostatic control system. How sleep need is sensed, integrated, and conveyed to downstream sleep circuits is poorly understood. Blum et al. find that Ca2+ transients in fly astrocytes correlate with time spent awake and identify molecular and circuit mechanisms underlying the generation, amplification, and transmission of these signals encoding sleep need.
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影响因子：
16.2
作者：
Agulhon, Cendra;Petravicz, Jeremy;McMullen, Allison B.;Sweger, Elizabeth J.;Minton, Suzanne K.;Taves, Sarah R.;Casper, Kristen B.;Fiacco, Todd A.;McCarthy, Ken D.
通讯作者：
McCarthy, Ken D.
DOI：
10.1126/science.aad4821
发表时间：
2016-04-29
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Ding F;O'Donnell J;Xu Q;Kang N;Goldman N;Nedergaard M
通讯作者：
Nedergaard M
影响因子：
5.3
作者：
Cao, Guan;Nitabach, Michael N.
通讯作者：
Nitabach, Michael N.
影响因子：
15.9
作者：
Garcia-Marin, Virginia;Garcia-Lopez, Pablo;Freire, Miguel
通讯作者：
Freire, Miguel
DOI：
10.1073/pnas.0308265100
发表时间：
2004-02-17
影响因子：
11.1
作者：
Angeli, D;Ferrell, JE;Sontag, ED
通讯作者：
Sontag, ED