Weekend Light Shifts Evoke Persistent Drosophila Circadian Neural Network Desynchrony.
Weekend Light Shifts Evoke Persistent Drosophila Circadian Neural Network Desynchrony.
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DOI：
10.1523/jneurosci.3074-19.2021
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发表时间：
2021-06-16
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影响因子：
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通讯作者：
Holmes TC
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作者：
Nave C;Roberts L;Hwu P;Estrella JD;Vo TC;Nguyen TH;Bui TT;Rindner DJ;Pervolarakis N;Shaw PJ;Leise TL;Holmes TC
我们开发了一种方法，用于培养的雄性成年果蝇大脑中的PERIOD（PER）蛋白和TIMELESS（TIM）振荡的单细胞分辨率纵向生物发光成像，该方法在模拟的日/夜周期下捕获昼夜节律电路范围的循环。光输入分析证实，昼夜光色素（CRY）是主要的昼夜光感受器，并介导恒定光（LL）的时钟中断，并且眼睛光输入对CRY是冗余的; 3小时光相位延迟（星期五），随后3小时光相位提前（周一早上）模拟周末熬夜的常见做法，周末晚些时候睡懒觉，然后在周一早上回到标准时间表[周末轻班（WLS）]。PER和TIM振荡是高度同步的所有主要的昼夜神经元亚组在11天的非移位光时间表。相比之下，WLS显着衰减PER振荡器的同步性和节律性在大多数昼夜神经元暴露期间和之后。侧腹神经元（LNv）振荡在WLS中最先去振荡，在WLS中最后去振荡。令人惊讶的是，背神经元组-3（DN 3）增加其组内同步响应WLS。在体内，WLS诱导睡眠稳定性、学习和记忆的暂时性缺陷，这些缺陷在时间上与电路损伤一致。我们的研究结果表明，WLS时间表在一周的大部分时间里破坏了整个电路的昼夜神经元振荡器同步，从而导致观察到的睡眠，学习和记忆行为缺陷。
We developed a method for single-cell resolution longitudinal bioluminescence imaging of PERIOD (PER) protein and TIMELESS (TIM) oscillations in cultured male adult Drosophila brains that captures circadian circuit-wide cycling under simulated day/night cycles. Light input analysis confirms that CRYPTOCHROME (CRY) is the primary circadian photoreceptor and mediates clock disruption by constant light (LL), and that eye light input is redundant to CRY; 3-h light phase delays (Friday) followed by 3-h light phase advances (Monday morning) simulate the common practice of staying up later at night on weekends, sleeping in later on weekend days then returning to standard schedule Monday morning [weekend light shift (WLS)]. PER and TIM oscillations are highly synchronous across all major circadian neuronal subgroups in unshifted light schedules for 11 d. In contrast, WLS significantly dampens PER oscillator synchrony and rhythmicity in most circadian neurons during and after exposure. Lateral ventral neuron (LNv) oscillations are the first to desynchronize in WLS and the last to resynchronize in WLS. Surprisingly, the dorsal neuron group-3 (DN3s) increase their within-group synchrony in response to WLS. In vivo, WLS induces transient defects in sleep stability, learning, and memory that temporally coincide with circuit desynchrony. Our findings suggest that WLS schedules disrupt circuit-wide circadian neuronal oscillator synchrony for much of the week, thus leading to observed behavioral defects in sleep, learning, and memory.