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.

睡眠处于稳态控制之下，因此增加的觉醒会产生睡眠需求并触发睡眠驱动。然而，人们对编码睡眠需求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⁺信号传导随着睡眠需要而增加。我们证明这种信号传导依赖于特定的 L 型 Ca ²⁺通道，并且是稳态睡眠反弹所必需的。生热增加 Ca ²⁺在星形胶质细胞中诱导持续的睡眠行为，我们利用这种表型对睡眠的稳态调节所需的基因进行遗传筛选。从这个大规模筛选中，我们确定了 TyrRII，这是星形胶质细胞中睡眠稳态所需的一种单胺能受体。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循环。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。这些发现定义了星形胶质细胞 Ca ²⁺ 编码睡眠的信号机制需要并揭示睡眠稳态控制系统的动态特性。