Your Brain Has a Temporal Clock: It Knows It's Summer

by Monica Joshi

That it's day or night, or even when to wake up: Your body knows it all. It even knows when you're lacking in iron, potassium, or magnesium, by making you crave certain foods (ahem, chocolate anyone?). Now, researchers at the RIKEN Brain Science Institute in Japan have discovered a key mechanism underlying how we and other animals keep track of seasons. Their study answers the age-old question: How do we know it's summer?

I remember watching Gilmore Girls and thinking that Lorelai was crazy for being able to smell “the first snow” in the air. This new study, published in Proceedings of the National Academy of Sciences, shows how the circadian clock machinery in the brain encodes seasonal changes, and could prove me wrong. Specifically, in the daytime, it tracks GABA activity along with changes in the amount of chloride located inside of certain neurons.

GABA, gamma-aminobutyric acid, is a biologically active substance found in plants and in brain and other animal tissues. In specific, it is a neurotransmitter that inhibits activation of neurons. As seasonal time-keeping is important for animals as well as people, it is important that we understand which part of the brain dictates this time-keeping. Recent studies have shown that it is accomplished by the same part of the brain that governs our daily circadian rhythms.

This brain area, called the suprachiasmatic nucleus (SCN), cyclically expresses certain "clock" genes during a 24-hour period. However, not all of the neurons march to the same beat. Two regions in the SCN are slightly out of phase, and as day length increases, so does the phase gap between them.

To understand how this happens, the researchers first measured expression levels of the clock gene Bmal1 in explanted dorsal and ventral SCNs of mice that had been living in long-day or short-day light cycles. The cyclical Bmal1 levels in dorsal and ventral regions from the long-day group were, as expected, out of phase. Those from the short-day group were synchronized. Modeling analysis predicted that coupling between the two regions is not a two-way street, and that this asymmetry causes the dorsal region to become out of phase when daylight increases.

Lead author Jihwan Myung explains, with regards to GABA's place in the whole system:

"GABA becomes excitatory when chloride levels inside neurons are high. We suspected that changes in GABA function across the SCN could represent the repulsive force that pushes these two clusters of neurons out of phase."

When the researchers blocked the GABA activity, the large phase gap seen in the long-day group disappeared. The cycles of Bmal1 levels came to resemble those of the short-day group, which was unaffected. This suggested to the team that GABA has a special effect on the dorsal SCN.

To test this hypothesis, they measured expression levels of two other genes that are responsible for importing and exporting chloride. Blocking chloride import abolished the phase gap seen in the long-day group, and as predicted by the model, even made SCNs trained on an even 12-hour daylight cycle resemble the short-day group.

Myung explained that:

"Just like in other animals, our bodies keep track of the seasons, and sudden changes in seasonal day length can cause severe mood disorder in some individuals. Understanding how to adjust our internal seasonal clock could lead to effective ways of helping people whose internal clocks have been disrupted."

The study could aid in finding new, interesting solutions to insomnia, sleep apnea, or even chronic fatigue syndrome.