Solomon H. Snyder Department of Neuroscience, Johns Hopkins University, Baltimore, MD 21205, USA.
Department of Neurology, Johns Hopkins University, Baltimore, MD 21205, USA.
Curr Biol. 2024 May 20;34(10):2186-2199.e3. doi: 10.1016/j.cub.2024.04.039. Epub 2024 May 8.
Animals exhibit rhythmic patterns of behavior that are shaped by an internal circadian clock and the external environment. Although light intensity varies across the day, there are particularly robust differences at twilight (dawn/dusk). These periods are also associated with major changes in behavioral states, such as the transition from arousal to sleep. However, the neural mechanisms by which time and environmental conditions promote these behavioral transitions are poorly defined. Here, we show that the E1 subclass of Drosophila evening clock neurons promotes the transition from arousal to sleep at dusk. We first demonstrate that the cell-autonomous clocks of E2 neurons primarily drive and adjust the phase of evening anticipation, the canonical behavior associated with "evening" clock neurons. We next show that conditionally silencing E1 neurons causes a significant delay in sleep onset after dusk. However, rather than simply promoting sleep, activating E1 neurons produces time- and light-dependent effects on behavior. Activation of E1 neurons has no effect early in the day but then triggers arousal before dusk and induces sleep after dusk. Strikingly, these activation-induced phenotypes depend on the presence of light during the day. Despite their influence on behavior around dusk, in vivo voltage imaging of E1 neurons reveals that their spiking rate and pattern do not significantly change throughout the day. Moreover, E1-specific clock ablation has no effect on arousal or sleep. Thus, we suggest that, rather than specifying "evening" time, E1 neurons act, in concert with other rhythmic neurons, to promote behavioral transitions at dusk.
动物表现出的行为节律模式受内部生物钟和外部环境的影响。尽管光强度在一天中不断变化,但在曙光(黎明/黄昏)时变化尤为明显。这些时期也与行为状态的重大变化相关,例如从觉醒到睡眠的转变。然而,时间和环境条件促进这些行为转变的神经机制还不清楚。在这里,我们表明果蝇傍晚时钟神经元的 E1 子类促进了黄昏时从觉醒到睡眠的转变。我们首先证明 E2 神经元的细胞自主时钟主要驱动和调整傍晚预期的相位,这是与“傍晚”时钟神经元相关的典型行为。我们接下来表明,条件性沉默 E1 神经元会导致黄昏后睡眠起始显著延迟。然而,激活 E1 神经元并不是简单地促进睡眠,而是对行为产生时间和光依赖性影响。激活 E1 神经元在当天早些时候没有效果,但随后会在黄昏前引起觉醒,并在黄昏后诱导睡眠。引人注目的是,这些激活诱导的表型依赖于白天的光照。尽管 E1 神经元对黄昏前后的行为有影响,但对 E1 神经元进行体内电压成像显示,其放电率和模式在一天中并没有显著变化。此外,E1 特异性时钟消融对觉醒或睡眠没有影响。因此,我们认为,E1 神经元不是指定“傍晚”时间,而是与其他节律神经元一起作用,促进黄昏时的行为转变。