Brown Matthew P, Verma Shubha, Palmer Isabelle, Zuniga Adler Guerrero, Rosensweig Clark, Keles Mehmet F, Wu Mark N
Solomon H. Snyder Department of Neuroscience, Johns Hopkins University, Baltimore, MD 21205, U.S.A.
Department of Neurology, Johns Hopkins University, Baltimore, MD 21205, U.S.A.
bioRxiv. 2023 Aug 29:2023.08.28.555147. doi: 10.1101/2023.08.28.555147.
Animals exhibit rhythmic patterns of behavior that are shaped by an internal circadian clock and the external environment. While 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 evening clock neurons promotes the transition from arousal to sleep at dusk. We first demonstrate that the cell-autonomous clocks of E2 neurons alone are required to 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 phenotypes critically depend on the presence of light during the day. Despite their influence on behavior around dusk, voltage imaging of E1 neurons reveals that their spiking rate does not vary between dawn and dusk. 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.
动物表现出由内部生物钟和外部环境塑造的节律性行为模式。虽然一天中光照强度会发生变化，但在黄昏（黎明/黄昏）时差异尤为显著。这些时段还与行为状态的重大变化相关，比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尚不清楚。在此，我们表明傍晚生物钟神经元的E1亚类在黄昏时促进从觉醒到睡眠的转变。我们首先证明，仅E2神经元的细胞自主生物钟就需要驱动和调整傍晚预期的相位，傍晚预期是与“傍晚”生物钟神经元相关的典型行为。接下来我们表明，有条件地沉默E1神经元会导致黄昏后睡眠开始显著延迟。然而，激活E1神经元对行为产生的影响并非简单地促进睡眠，而是具有时间和光照依赖性。E1神经元在一天早些时候激活没有效果，但在黄昏前会引发觉醒，在黄昏后会诱导睡眠。令人惊讶的是，这些表型严重依赖于白天光照的存在。尽管E1神经元对黄昏前后的行为有影响，但对其进行电压成像显示，它们的放电率在黎明和黄昏之间没有变化。此外，特异性敲除E1的生物钟对觉醒或睡眠没有影响。因此，我们认为，E1神经元并非确定“傍晚”时间，而是与其他节律性神经元协同作用，在黄昏时促进行为转变。
