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Institute of Pharmacology and Toxicology Chronobiology and Sleep Research

The Organization of Circadian Clocks in Animals

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Metazoans from Drosophila to humans possess circadian clocks in most cells of the body. As mentioned above, each of these clocks is cell-autonomous – it is capable of functioning without input from any other cells (Welsh et al., 1995). Nevertheless, the period length of such clocks is only approximately 24 hours. Hence, the cells must be synchronized regularly with one another and with the environment. For many transparent and semi-transparent organisms (from bacteria to zebrafish), light can entrain the rhythms of each cell directly (e.g. Plautz et al., 1997; Whitmore et al., 2000).

In higher vertebrates, however, this synchronization is a hierarchical process. A master clock – the suprachiasmatic nucleus (SCN) of the hypothalamus in mammals – communicates timing information to most cells of the body via a range of direct and indirect cues (body temperature, feeding time, and circulating hormones such as glucocorticoids). The SCN itself is synchronized to light-dark cycles via the retionohypothalamic tract in a strictly ocular mechanism involving multiple photoreceptors (reviewed in Ben-Schlomo and Kyriacou, 2002). Finally, a subset of genes in some peripheral tissues can bypass this hierarchical signaling and directly respond to acute light stimulation communicated via the parasympathetic nervous system (Ishida et al., 2005). This organisation is depicted below in Figure 2.

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Figure 2. Hierarchical organization of circadian clocks. Although each cell possesses a cell-autonomous circadian oscillator, these oscillators must be synchronized to the light of the outside world. In lower organisms, this process happens independently in each tissue. In higher vertebrates, however, peripheral oscillators are synchronized by a central clock which is itself entrained by light.

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Ben-Shlomo, R., and Kyriacou, C. P. (2002). Circadian rhythm entrainment in flies and mammals. Cell Biochem Biophys 32: 141-156.

Ishida, A., Mutoh, T., Ueyama, T., Bando, H., Masubuchi, S., Nakahara, D., Tsujimoto, G., and Okamura, H. (2005). Light activates the adrenal gland: timing of gene expression and glucocorticoid release.Cell Metab 2:297-307.

Plautz, J. D., Kaneko, M., Hall, J. C., and Kay, S. A. (1997). Independent photoreceptive circadian clocks throughout Drosophila. Science 278:1632-1635.

Welsh, D. K., Logothetis, D. E., Meister, M., and Reppert, S. M. (1995). Individual neurons dissociated from rat suprachiasmatic nucleus express independently phased circadian firing rhythms. Neuron 14:697-706

Whitmore, D., Foulkes, N. S., and Sassone-Corsi, P. (2000). Light acts directly on organs and cells in culture to set the vertebrate circadian clock. Nature 404: 87-91.

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