HHMI, University of Pennsylvania, Philadelphia, PA 19104.
Chronobiology and Sleep Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.
Proc Natl Acad Sci U S A. 2021 Nov 23;118(47). doi: 10.1073/pnas.2111183118.
Sleep is controlled by homeostatic mechanisms, which drive sleep after wakefulness, and a circadian clock, which confers the 24-h rhythm of sleep. These processes interact with each other to control the timing of sleep in a daily cycle as well as following sleep deprivation. However, the mechanisms by which they interact are poorly understood. We show here that neurons, previously identified as neurons that function downstream of the clock to regulate rhythms of locomotor activity, are also targets of the sleep homeostat. Sleep deprivation decreases activity of neurons, likely to suppress circadian-driven activity during recovery sleep, and ablation of neurons promotes sleep increases generated by activation of the homeostatic sleep locus, the dorsal fan-shaped body (dFB). Also, mutations in peptides produced by the locus increase recovery sleep following deprivation. Transsynaptic mapping reveals that neurons feed back onto central clock neurons, which also show decreased activity upon sleep loss, in a Hugin peptide-dependent fashion. We propose that neurons integrate circadian and sleep signals to modulate circadian circuitry and regulate the timing of sleep.
一种是基于稳态的机制,该机制会在清醒后引发睡眠;另一种是昼夜节律钟,它赋予睡眠 24 小时的节奏。这两种机制相互作用,控制着睡眠在日常周期中的时间以及在睡眠剥夺后的时间。然而,它们相互作用的机制尚不清楚。我们在这里表明,先前被确定为时钟下游调节运动活动节律的神经元,也是睡眠稳态的靶点。睡眠剥夺会降低神经元的活动,可能会在恢复性睡眠期间抑制由昼夜节律驱动的活动,而 神经元的消融会促进由稳态睡眠中枢(背扇形体)激活引起的睡眠增加。此外,由 基因座产生的肽的突变会增加剥夺后的恢复性睡眠。转导性映射表明,神经元以 Hugin 肽依赖的方式反馈到中央时钟神经元,而中央时钟神经元在睡眠缺失时也表现出活性降低。我们提出,神经元整合昼夜节律和睡眠信号,以调节昼夜节律回路并调节睡眠的时间。