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An intact pituitary vasopressin system is critical for building a robust circadian clock in the suprachiasmatic nucleus.

ABSTRACT: The circadian clock is a biological timekeeping system that oscillates with a circa-24-h period, reset by environmental timing cues, especially light, to the 24-h day-night cycle. In mammals, a "central" clock in the hypothalamic suprachiasmatic nucleus (SCN) synchronizes "peripheral" clocks throughout the body to regulate behavior, metabolism, and physiology. A key feature of the clock's oscillation is resistance to abrupt perturbations, but the mechanisms underlying such robustness are not well understood. Here, we probe clock robustness to unexpected photic perturbation by measuring the speed of reentrainment of the murine locomotor rhythm after an abrupt advance of the light-dark cycle. Using an intersectional genetic approach, we implicate a critical role for arginine vasopressin pathways, both central within the SCN and peripheral from the anterior pituitary.

SUBMITTER: Yamaguchi Y

PROVIDER: S-EPMC10614613 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature

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An intact pituitary vasopressin system is critical for building a robust circadian clock in the suprachiasmatic nucleus.

Yamaguchi Yoshiaki Y Maekawa Yota Y Kabashima Kyohei K Mizuno Takanobu T Tainaka Motomi M Suzuki Toru T Dojo Kumiko K Tominaga Takeichiro T Kuroiwa Sayaka S Masubuchi Satoru S Doi Masao M Tominaga Keiko K Kobayashi Kazuto K Yamagata Satoshi S Itoi Keiichi K Abe Manabu M Schwartz William J WJ Sakimura Kenji K Okamura Hitoshi H

Proceedings of the National Academy of Sciences of the United States of America 20231016 43

The circadian clock is a biological timekeeping system that oscillates with a circa-24-h period, reset by environmental timing cues, especially light, to the 24-h day-night cycle. In mammals, a "central" clock in the hypothalamic suprachiasmatic nucleus (SCN) synchronizes "peripheral" clocks throughout the body to regulate behavior, metabolism, and physiology. A key feature of the clock's oscillation is resistance to abrupt perturbations, but the mechanisms underlying such robustness are not wel ...[more]

PMID: 37844254

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Project description:The biological master clock, suprachiasmatic nucleus (of rat and mouse), is composed of ~10,000 clock cells which are heterogeneous with respect to their circadian periods. Despite this inhomogeneity, an intact SCN maintains a very good degree of circadian phase (time) coherence which is vital for sustaining various circadian rhythmic activities, and it is supposedly achieved by not just one but a few different cell-to-cell coupling mechanisms, among which action potential (AP)-mediated connectivity is known to be essential. But, due to technical difficulties and limitations in experiments, so far very little information is available about the morphology of the connectivity at a cellular scale. Building upon this limited amount of information, here we exhaustively and systematically explore a large pool (~25,000) of various network morphologies to come up with some plausible network features of SCN networks. All candidates under consideration reflect an experimentally obtained 'indegree distribution' as well as a 'physical range distribution of afferent clock cells.' Then, importantly, with a set of multitude criteria based on the properties of SCN circadian phase waves in extrinsically perturbed as well as in their natural states, we select out appropriate model networks: Some important measures are, 1) level of phase dispersal and direction of wave propagation, 2) phase-resetting ability of the model networks subject to external circadian forcing, and 3) decay rate of perturbation induced "phase-singularities." The successful, realistic networks have several common features: 1) "indegree" and "outdegree" should have a positive correlation; 2) the cells in the SCN ventrolateral region (core) have a much larger total degree than that of the dorsal medial region (shell); 3) The number of intra-core edges is about 7.5 times that of intra-shell edges; and 4) the distance probability density function for the afferent connections fits well to a beta function. We believe that these newly identified network features would be a useful guide for future explorations on the very much unknown AP-mediated clock cell connectome within the SCN.

Dataset Information

An intact pituitary vasopressin system is critical for building a robust circadian clock in the suprachiasmatic nucleus.

Publications

An intact pituitary vasopressin system is critical for building a robust circadian clock in the suprachiasmatic nucleus.

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