Seasonal and daily rhythms are generated by signals from a central biological clock in the brains of humans and other animals, which runs in sync with the 24-hour cycle of light and darkness. Circadian rhythms help the body prepare for anticipated changes in the environment and optimize the timing of sleep, eating, and other daily activities.
Disruption of the biological clock
Some people experience a number of negative consequences if their circadian rhythms are disrupted, including daytime fatigue, hormonal changes, digestive issues, mood swings, and more. That’s why understanding these circadian rhythms is important.
Scientists at Washington University in St. Louis are working to unravel the mystery of how our internal biological clocks keep time, and their new research, published July 24 in the Proceedings of the National Academy of Sciences, helps answer long-standing questions about how circadian rhythms are generated and maintained.
How does the biological clock work?
In all mammals, signals for daily circadian rhythms come from a small part of the brain called the suprachiasmatic nucleus. Several previous studies from the University of Washington and other institutions have sought to determine whether a neurotransmitter called gamma-aminobutyric acid, or GABA, plays a role in synchronizing daily rhythms among individual SCN cells. However, the role of GABA in the SCN has remained unclear.
The chemical interventions introduced by Daniel Granados Fontes, PhD, a researcher in the College of Arts and Sciences and a researcher in the lab of biologist Eric Herzog and lead author of the new study, and other scientists did not appear to significantly change the way neurons in the suprachiasmatic nucleus fire or affect the daily rhythmic regulation of actual behavior in mice.
A different approach
So Granados Fontes and his team took a different approach, changing the expression of two types of GABA receptors to see if receptor density had any effect on synchronization or behavior.
“Controlling the number of receptors is important for regulating physiological processes such as learning and memory, but not circadian rhythms,” Granados says. But in this case, changing the density of gamma-2 or delta-type GABA receptors had a dramatic effect: Reducing or mutating these receptors in the suprachiasmatic nucleus of mice reduced the synchrony of their circadian rhythms by a third, and the mice in the study increased their daytime wheel running and reduced their normal nighttime running.
Overexpression of one type of GABA receptor compensated for the loss of the other, suggesting that the two types of receptors may perform a similar function in the suprachiasmatic nucleus, even though they facilitate different processes within the body, Granados said.
“These results open up the possibility of understanding whether changes in GABA receptor density are important for regulating seasonal responses,” Granados says. “For example, how do animals in nature respond to summer when days are long or winter when days are short?”