November 8, 1999

Exercise Makes Mice Smarter, Salk Scientists Demonstrate

Salk News

Exercise Makes Mice Smarter, Salk Scientists Demonstrate

La Jolla, CA – Should you hit the treadmill before hitting the books?

A new Salk study shows that physical exercise triggers chemical changes in the brain that spur learning – at least in mice. Associated work suggests that similar mechanisms may operate in humans as well.

The findings build on earlier work showing that exercise boosts the number of brain cells in the hippocampus, the part of the brain known to be centrally important in learning and memory.

“The question remained, though, whether the addition of neurons correlated with increased brain function,” said Salk Professor Fred H. Gage, senior author of the study, which appears in the current issue of the Proceedings of the National Academy of Sciences. “The new study indicates that two measures of brain activity are changed; one behavioral, the other electrophysiological.”

In the current study, mice were separated into two groups. One group was housed in standard cages with food and water only; the second group had access to a running wheel.

“Given the opportunity, mice love to run,” explained Henriette van Praag, a Salk postdoctoral fellow and co-first author on the study. “The mice in our study ran an average of five kilometers a night.”

After approximately six weeks in the two environments, the mice were tested for their ability to learn the site of a hidden platform in a water maze. The mice who ran learned significantly better than their sedentary counterparts.

“It’s important to note that the mice were genetically identical,” said van Praag, “so we know that the difference we observed was due to the difference in their environments.”

The brains from both sets of mice were examined for their abilities to undergo long-lasting and rapidly acting changes in the way that cells communicate with each other called LTP (long term potentiation).

“LTP may be the molecular basis for how long-term memories are initiated,” said Salk Professor Terrence Sejnowski, co-author of the study. “So the discovery that running mice are capable of sustaining stronger LTP than sedentary mice may be one of the reasons they learn more readily.”

Both groups of mice were given a dye, BrdU (bromodeoxyuridine), that labels dividing cells. When their brains were examined for new cell growth in the hippocampus, the mice on the move had grown more cells than their litter mates.

“As expected from the previous work, we saw abundant production of new cells,” said Gage, “and importantly, this time we showed that many of those cells are neurons, the class specialized to transmit messages throughout the brain.”

What is the connection between fleet feet and blooming brains?

Physiologists know that exercise affects steroid hormone and stress levels, so the Salk team looked at levels of corticosterone in the blood of both sets of mice. No differences were seen, however.

A study Gage’s group published in November 1998, in collaboration with Swedish colleagues at the Salgrenska University Hospital, Göteburg, was the first to demonstrate that adult humans grow new brain cells, overturning years of dogma that stated we are born with all the brain cells we will ever have and only lose cells during our lives.

“What I find most exciting,” Gage adds, “is that taken together the studies suggest that throughout one’s life, one’s behavior can change the structure of the brain, and that these changes can in turn affect how we behave in our environment.”

Co-first author of the study is Brian R. Christie, a postdoctoral fellow in Sejnowski’s laboratory. The study, titled “Running enhances neurogenesis, learning and long-term potentiation in mice,” was supported by the National Institute of Aging, the National Institute of Neurological Disorders and Stroke, the Lookout Fund, the Pasarow Foundation, the Hollfelder Foundation and the American Paralysis Association.

The Salk Institute for Biological Studies, located in La Jolla, Calif., is an independent nonprofit institution dedicated to fundamental discoveries in the life sciences, the improvement of human health and conditions, and the training of future generations of researchers. The Institute was founded in 1960 by Jonas Salk, M.D., with a gift of land from the City of San Diego and the financial support of the March of Dimes Birth Defects Foundation. Website:

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