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How the Brain Resets Its Biological Clock

/ Source: LiveScience

The brain's internal clock keeps time via a synchronized network of cells that is able to reset itself, a new study reveals.

This resetting may be what enables us to change our own daily rhythms with the seasons while the clock itself remains fairly stable, the researchers report.

But this mechanism didn't evolve to deal with modern technologies, such as alarm clocks or air travel. Messing with natural daily cycles can cause jetlag, or more serious effects. Shift work, for instance, has been linked to metabolic disorders such as diabetes, and even diseases like cancer.

"Shift work is now listed as a potential carcinogen by the World Health Organization," said study researcher Erik Herzog, a biologist at Washington University in St. Louis. By understanding how the brain's clock is wired, researchers could develop ways to improve the brain's ability to deal with these kinds of environmental perturbations, so they have fewer detrimental effects on our health, Herzog told LiveScience. [ 10 Things You Didn't Know About the Brain ]

The brain's timing center is called the suprachiasmatic nucleus, or SCN. "Each cell is its own little timer," which works by turning on and off a set of "clock genes" that tell the cell to make proteins, Herzog explained. These genes operate on an approximately 24-hour cycle, known as a circadian rhythm. These cycles are important for regulating metabolism, hormone release and sleep/waking cycles.

Signaling between cells within the SCN is thought to set the brain's clock. To find out how these cells were connected, Herzog and his colleagues used electrodes to record signals from about 100 neurons in a lab dish. 

The researchers found that a signaling chemical in the brain, called gamma-aminobutyric acid ( GABA ), has a desynchronizing effect on the cells within the clock, allowing it to make small adjustments — for example, during changes in day length across seasons, the researchers suspect.

"If a whole bunch of clocks that are tightly wired together, like pendula clocks connected by wooden boards, then any mistake in a clock would be hard to correct," Herzog said.

Even though the SCN cells were physically connected to many others, the electrical activity of each neuron did not seem to affect others much. Herzog described the interactions using a Facebook analogy: A person may have many Facebook friends but only interacts with a few on a regular basis.

The researchers also measured the activation of clock genes in real time. In mice, they inserted a gene that makes fireflies glow, so that when the mouse's clock genes turned on or off, the glowing gene also turned on or off. Using a sensitive camera, the researchers watched these genes "blinking" on a daily cycle. When they blocked the GABA signaling system with drugs, the blinking became more precise, reinforcing the idea that this system disturbs the brain's clock.

Of course, the brain's clock must somehow be synchronized in the first place. Herzog and his colleagues previously found that a brain chemical called vasoactive intestinal polypeptide (VIP) does this job. However, future work is needed to map the brain's VIP signaling system.

Together, the VIP and the GABA systems keep the brain's clock accurate while allowing it to reset itself in different environments, the researchers reported today (June 5) in the journal Neuron.

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