Network-driven intracellular cAMP coordinates circadian rhythm in the suprachiasmatic nucleus

Daisuke Ono; Huan Wang; Chi Jung Hung; Hsin-Tzu Wang; Naohiro Kon; Akihiro Yamanaka; Yulong Li; Takashi Sugiyama

doi:10.1126/sciadv.abq7032

Network-driven intracellular cAMP coordinates circadian rhythm in the suprachiasmatic nucleus

Sci Adv. 2023 Jan 4;9(1):eabq7032. doi: 10.1126/sciadv.abq7032. Epub 2023 Jan 4.

Authors

Daisuke Ono^{1

2}, Huan Wang³, Chi Jung Hung^{1

2}, Hsin-Tzu Wang^{4

5

6}, Naohiro Kon^{4

5}, Akihiro Yamanaka⁷, Yulong Li³, Takashi Sugiyama⁸

Affiliations

¹ Department of Neuroscience II, Research Institute of Environmental Medicine, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan.
² Department of Neural Regulation, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
³ State Key Laboratory of Membrane Biology, Peking University School of Life Sciences, Beijing, China.
⁴ Institute of Transformative Bio-Molecules (WPI-ITbM), Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan.
⁵ Laboratory of Animal Integrative Physiology, Graduate School of Bioagricultural Sciences, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan.
⁶ Department of Biological Sciences, School of Science, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033, Japan.
⁷ Chinese Institute for Brain Research (CIBR), Beijing, 102206, China.
⁸ Advanced Optics and Biological Engineering, Evident Corporation, Tokyo, Japan.

PMID: 36598978
DOI: 10.1126/sciadv.abq7032

Abstract

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 Ca²⁺, 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.