Tired from your red-eye flight from LA to NYC? You should probably blame GABA, a chemical in the brain that neuroscientists from St. Louis have found responsible for resetting the brain's daily biological clock and doing a poor job of it.

Timing of our internal clock - known as the circadian rhythm - is exceptionally accurate and is an almost exact parallel with the 24-hour day, varying by only a few minutes each day.

"These synchronized networks are very precise," said lead author Dr. Eric Herzog, a biologist at Washington University in St. Louis. "If you let them free-run in constant darkness they will lose or gain only a few minutes out of the 1,440 minutes in a day. So they're accurate to within 1 or 2 percent."

When sunlight reaches our eyes in the morning, a network of nerve cells - or neurons - kick into gear to trigger a cascade of events that regulate hunger, alertness, and variety of other behaviors connected to being awake. But like an hour glass, the cellular cascade slowly ticks down until nighttime, when the same network of neurons switches gears and induces feelings of sleep and tiredness.

The neurons responsible for setting this accuracy live in two, small wing-like structures in the brain called the suprachiasmatic nucleus (SCN).

To keep the pace of clock, the 20,000 neurons in the SCN work in harmony, like the metronomes in the following video (you may want to lower the volume).

Dish Clock

Herzog's team made their discovery by recreating the SCN clock from a mouse in a petri dish. Clock neurons from mice share many of the same features as human SCN neurons and are considered a good model.

One of Herzog's Ph.D. students, Mark Freeman, developed a new method for simultaneously measuring the activity of 100 clock neurons placed in this dish.

"The neurons will attach to the electrodes [in the dish], creating a clock in a dish that will tick away for weeks or months," said Herzog.

Their main goal was to learn how this clock is wired.

"It wasn't clear, for example, if each neuron communicated with just a few of its neighbors or with all of them," said Herzog

In 2005, Herzog's team reported that clock neurons communicate with each other via brain hormone called VIP.

In the present study, when VIP was added to clock neurons in a dish, the brain hormone forced the clock neurons to harmonize with each other. The researchers found that VIP alters the production of circadian genes "to speed up or slow down neurons until they are all in sync."

Reset Button

Each SCN neuron has its own natural rhythm, like the metronomes at the beginning of the video, but the neurons are also forced to align when they join the clock network and are exposed to VIP.

However, when we travel between time zones, our brains need to reset our internal clocks to matchup with slight difference in light schedule.

In this study, the researchers found a brain chemical called GABA breaks the synchrony of clock neurons, which allows them to adjust their pace. GABA is a neurotransmitter or a compound that carries signals between individual neurons.

"We think the GABA network is there to let our clocks adjust to environmental cues, such as gradual, seasonal changes in sunrise and sunset," said Herzog.

GABA counteracts the actions of VIP by allowing some neurons to change their pace, which Herzog describes as 'adding jitter' to the clock.

"But there isn't enough jitter in the clock to allow it to make abrupt adjustments, such as the one-hour forward jump when Daylight Savings Time starts," said Herzog. "That "spring forward" has been statistically shown to increase the likelihood of heart attacks and car accidents."

Source: Freeman Jr GM, Krock RM, Aton SJ, Thaben P, Herzog ED. GABA Networks Destabilize Genetic Oscillations in the Circadian Pacemaker. Neuron. 2013.

Published by Medicaldaily.com