Jiang Ruihan, Tian Yue, Yuan Xin, Guo Fang
Department of Neurobiology, Department of Neurology of Sir Run Run Shaw Hospital and School of Brain Science and Brain Medicine, Zhejiang University School of Medicine, Hangzhou 310058, China; MOE Frontier Science Center for Brain Research and Brain-Machine Integration, State Key Laboratory of Brain-machine Intelligence, Zhejiang University, 1369 West Wenyi Road, Hangzhou 311121, China; NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University, Hangzhou 310058, China.
Department of Neurology of Children's Hospital and School of Brain Science and Brain Medicine, Zhejiang University School of Medicine, Hangzhou 310058, China; MOE Frontier Science Center for Brain Research and Brain-Machine Integration, State Key Laboratory of Brain-machine Intelligence, Zhejiang University, 1369 West Wenyi Road, Hangzhou 311121, China; NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University, Hangzhou 310058, China.
Curr Biol. 2025 Apr 21;35(8):1750-1764.e3. doi: 10.1016/j.cub.2025.02.056. Epub 2025 Mar 18.
Circadian neurons form a complex neural network that generates circadian oscillations. How the circadian neural network transmits circadian signals to other brain regions, thereby regulating the activity patterns in fruit flies, is not well known. Using the FlyWire database, we identified a cluster of descending neurons, DNp27, which is densely connected with key circadian neurons and the visual circuit, projecting extensively across the brain. DNp27 receives excitatory inputs from the circadian neurons DN3s at night and photo-inhibitory signals predominantly during the day, resulting in calcium oscillations that peak in the early morning and dip at dusk. Experimental manipulation of DNp27 revealed its role in activity regulation: artificial activation of DNp27 decreased flies' activity, while ablation or silencing led to an advance in the morning anticipatory peak. Similar alterations in the morning peak were observed following pan-neuronal knockdown of either Trissin or TrissinR, suggesting the involvement of this neuropeptide signaling pathway in DNp27 function. Moreover, neural circuitry and connectivity analyses indicate that DNp27 may regulate circadian neurons via extra-clock electrical oscillators (xCEOs). Lastly, we found that DNp27 modulates arousal thresholds by inhibiting light-responsive activity in the central brain, thereby promoting sleep stability, particularly in the pre-dawn period. Together, these findings suggest that DNp27 plays a crucial role in maintaining stable sleep patterns.
昼夜节律神经元形成一个产生昼夜节律振荡的复杂神经网络。昼夜节律神经网络如何将昼夜节律信号传递到其他脑区，从而调节果蝇的活动模式，目前尚不清楚。利用FlyWire数据库，我们鉴定出一群下行神经元DNp27，它与关键的昼夜节律神经元和视觉回路紧密相连，广泛投射于整个大脑。DNp27在夜间接收来自昼夜节律神经元DN3s的兴奋性输入，主要在白天接收光抑制信号，导致钙振荡在清晨达到峰值，在黄昏时下降。对DNp27的实验操作揭示了其在活动调节中的作用：人工激活DNp27会降低果蝇的活动，而消融或沉默则会导致早晨预期峰值提前。在Trissin或TrissinR的全神经元敲低后，观察到早晨峰值有类似变化，表明该神经肽信号通路参与了DNp27的功能。此外，神经回路和连接性分析表明，DNp27可能通过时钟外电振荡器（xCEO）调节昼夜节律神经元。最后，我们发现DNp27通过抑制中脑的光反应活动来调节觉醒阈值，从而促进睡眠稳定性，尤其是在黎明前阶段。总之，这些发现表明DNp27在维持稳定睡眠模式中起着关键作用。
