
After three years of work, Washington University researchers have identified what they say is a primary factor in mammalian brain cells which keeps cells in sync.
Associate professor of Biology Erik Herzog and his team measured the abundance of a protein called cFOS, an indicator of neural activity, in the olfactory bulbs (OB) of mice.
The component is considered to be a critical factor in controlling circadian rhythms.
Circadian rhythms control many bodily functions, such as sleep cycles and hormone secretions.
“We found cFOS levels increase dramatically when mice smell an odor like cedar oil. cFOS induction doubled when the odor was presented at night,” explained Herzog. “Importantly, the rhythm in the OB was required for a rhythm in other parts of the brain serving olfaction.”
Although it has long been scientific consensus that the brain is responsible for daily scheduling, it was not known which region specifically governed the schedule.
The discovery clarifies the roles that vasoactive intestinal polypeptides (VIP) and the neurotransmitter GABA play in synchronizing biological clocks and reveals how mammals regulate circadian rhythm.
Neurons in the biological clock, an area called the suprachiasmatic nucleus (SCN), are located at the base of the brain right across the optic nerve. They keep 24-hour time and are normally highly synchronized.
“The OB receive information about odors in the environment,” said Herzog. “Importantly the rhythm in the OB persisted in mice lacking their SCN or daily rhythms in all the other behaviors we typically measure.”
The SCN is composed of over 20,000 neurons; together these neurons are intrinsic clocks in communication with each other to keep 24-hour time.
It was previously believed that GABA was the prime candidate for the rallying role.
Herzog said, however, that GABA was not needed and VIP synchronizes even when GABA signals were blocked.
Notably, one member of the research team, senior Alan Tseng, was an undergraduate. Tseng began to work with Herzog during his freshman year, because of Herzog’s specialty.
“I wanted a mentor during the summer of my freshman year, so I found Professor Herzog along with a few other choices on the biology faculty listing,” stated Tseng. “I chose Professor Herzog’s lab because I was always interested in neurology.”
Although he admits feeling uneasy at first, Tseng feels fortunate that he has gained this valuable experience.
“Since I started as a freshman, I was definitely intimidated. But under their [Herzog and other post-doctoral students] tutelage and guidance, I learned to understand most of the language they used to present their project data at lab meetings,” said Tseng.
Tseng advises students to stick to one lab in order to gain the best experience.
“The more I worked in the lab, the more involved in the project I became, and consequently, Professor Herzog gave me larger and larger responsibilities,” stated Tseng. “In the end, I think it’s dedication and loyalty to one project that produces the most rewarding experience.”
The research team, consisting of Herzog, postdoctoral researcher Daniel Grandos-Fuentes, and Tseng, published their results in the Nov. 27-Dec. 1 online issue of the Proceedings of the National Academy of Sciences.