How biological clocks communicate with each other

Multiple biological clocks control the daily rhythms of physiology and behavior in animals and humans. Whether and how these clocks are connected with each other is still a largely open question. A new study now shows that a central clock governs the decentral, circadian rhythms in certain cases.

Whether fly, mouse or human, circadian clocks are the central mechanisms that drive circadian rhythms in all animals. However, the notion of one, central clock regulating the timing of all the body's processes is not true. Rather, most organisms have a multitude of circadian clocks: a central clock in the brain and various peripheral clocks in the organs and systems.

Yet, it is still largely unknown how these clocks communicate with each other, how they synchronize and whether the central clock sets the time for all other units. An international team of scientists from the University of Würzburg and the Universidad de Valparaiso (Chile) recently shed light on the link between a central and peripheral clock in the fruit fly and provided experimental proof of the so-called "coupled-oscillator model" comprising a "master" clock and multiple "slave clocks".

In their search for the connecting pathway, the Würzburg scientists concentrated on specific neurons that could facilitate the contact between the central and the peripheral clock, the so-called PTTH neurons. "They should be ideally suited to connect the clocks just because of their spatial arrangement," says Christian Wegener.

In fact, the Würzburg scientists were able to show that the PTTH neurons establish a direct link between the brain-based clock of the fruit fly and its peripheral counterpart. They showed in experiments that the central clock neurons produce a special neuropeptide which transmits time information to the PTTH neurons. The PTTH neurons in turn forward the information to the pacemaker of the prothoracic gland and regulate the production of ecdysone.

The Würzburg researchers found their master and slave theory confirmed by the work of their Chilean colleagues. The researchers in Chile had conducted a number of experiments in which they had artificially slowed down the circadian clocks of Drosophila in various combinations and observed the impact on the hatching behaviour.

The results: When both clocks run more slowly, the "hatching rhythm" increases from normally 24 hours to over 27. A similar effect is observed when the peripheral clock continues to run at regular speed and the central clock is slowed down. Vice versa, however – i.e. normal working central clock and slowed down peripheral clock – the hatching behaviour remains unchanged at a 24-hour interval.

"This is the first comprehensive experimental description of a pathway that links circadian clocks and it shows that the coupled-oscillator model is actually true in certain cases," says Christian Wegener. But he admits that science is still a long way from understanding the exact interactions of the circadian clocks. After all, the recent findings illustrate that the diverse mechanisms are heavily interwoven and provided with feedback loops. So Wegener is certain that "it is not going to be easy".

Source: Universität Würzburg

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