Fan Yaqian, Tian Yao, Han Junhai
School of Life Science and Technology, The Key Laboratory of Developmental Genes and Human Disease, Southeast University, Nanjing, 210096, China.
Co-innovation Center of Neuroregeneration, Nantong University, Nantong, 226000, China.
Neurosci Bull. 2025 Apr 30. doi: 10.1007/s12264-025-01397-1.
Sleep, an essential and evolutionarily conserved behavior, is regulated by numerous neurotransmitter systems. In mammals, glutamate serves as the wake-promoting signaling agent, whereas in Drosophila, it functions as the sleep-promoting signal. However, the precise molecular and cellular mechanisms through which glutamate promotes sleep remain elusive. Our study reveals that disruption of glutamate signaling significantly diminishes nocturnal sleep, and a neural cell-specific knockdown of the glutamate-gated chloride channel (GluClα) markedly reduces nocturnal sleep. We identified two pairs of neurons in the ventral nerve cord (VNC) that receive glutamate signaling input, and the GluClα derived from these neurons is crucial for sleep promotion. Furthermore, we demonstrated that GluClα mediates the glutamate-gated inhibitory input to these VNC neurons, thereby promoting sleep. Our findings elucidate that GluClα enhances nocturnal sleep by mediating the glutamate-gated inhibitory input to two pairs of VNC neurons, providing insights into the mechanism of sleep promotion in Drosophila.
睡眠是一种必不可少且在进化上保守的行为，受众多神经递质系统调节。在哺乳动物中，谷氨酸作为促进清醒的信号传导剂，而在果蝇中，它则作为促进睡眠的信号。然而，谷氨酸促进睡眠的确切分子和细胞机制仍不清楚。我们的研究表明，谷氨酸信号传导的破坏会显著减少夜间睡眠，并且谷氨酸门控氯离子通道（GluClα）在神经细胞中的特异性敲低会显著减少夜间睡眠。我们在腹神经索（VNC）中鉴定出两对接收谷氨酸信号输入的神经元，并且源自这些神经元的GluClα对促进睡眠至关重要。此外，我们证明GluClα介导对这些VNC神经元的谷氨酸门控抑制性输入，从而促进睡眠。我们的研究结果阐明，GluClα通过介导对两对VNC神经元的谷氨酸门控抑制性输入来增强夜间睡眠，为果蝇中促进睡眠的机制提供了见解。
