Department of Neuroscience II, Research Institute of Environmental Medicine, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan.
Department of Neural Regulation, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
Sci Adv. 2023 Jan 4;9(1):eabq7032. doi: 10.1126/sciadv.abq7032.
The mammalian central circadian clock, located in the suprachiasmatic nucleus (SCN), coordinates the timing of physiology and behavior to local time cues. In the SCN, second messengers, such as cAMP and Ca, are suggested to be involved in the input and/or output of the molecular circadian clock. However, the functional roles of second messengers and their dynamics in the SCN remain largely unclear. In the present study, we visualized the spatiotemporal patterns of circadian rhythms of second messengers and neurotransmitter release in the SCN. Here, we show that neuronal activity regulates the rhythmic release of vasoactive intestinal peptides from the SCN, which drives the circadian rhythms of intracellular cAMP in the SCN. Furthermore, optical manipulation of intracellular cAMP levels in the SCN shifts molecular and behavioral circadian rhythms. Together, our study demonstrates that intracellular cAMP is a key molecule in the organization of the SCN circadian neuronal network.
哺乳动物的中枢生物钟位于视交叉上核（SCN），将生理和行为的时间与当地时间线索协调一致。在 SCN 中，第二信使，如 cAMP 和 Ca2+，被认为参与分子生物钟的输入和/或输出。然而，第二信使的功能作用及其在 SCN 中的动态仍然很大程度上不清楚。在本研究中，我们可视化了 SCN 中第二信使和神经递质释放的昼夜节律的时空模式。在这里，我们表明神经元活动调节 SCN 中血管活性肠肽的节律性释放，从而驱动 SCN 中细胞内 cAMP 的昼夜节律。此外，SCN 中细胞内 cAMP 水平的光学操纵会改变分子和行为的昼夜节律。总之，我们的研究表明细胞内 cAMP 是 SCN 昼夜节律神经网络组织的关键分子。
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