New neurons (white) integrating into hippocampus.JASON SNYDER
Adult mice that exercised on a running wheel after experiencing an event were
more likely than their inactive mates to forget the experience,
according to a paper from researchers at the University of Toronto,
published in Science today (May 8). The results suggest that the production of new
neurons—neurogenesis—prompted by the exercise wiped out the mice’s
memories. They might also explain why human infants, whose brains
exhibit abundant neurogenesis, do not have long-term memories.
“In general, hippocampal neurogenesis has been thought to be the basis
for memory and they’re suggesting that it’s the basis for amnesia,” said
Thomas Insel, director of the National Institute of Mental Health. “That’s a very controversial and provocative concept.”
Infantile amnesia is common to all humans. Children typically do not
develop long-term memories until age three or four. But why is that? Sheena Josselyn and her husband Paul Frankland,
who are both neuroscientists at the University of Toronto, pondered
precisely that question after noticing that their two-year-old daughter
could easily remember things that happened within a day or two, but not
several months in the past.
More specifically, they wondered whether it might have something to do
with neurogenesis in the hippocampus—a brain region involved in learning
and memory. Hippocampal neurons are produced rapidly during infancy,
but neuronal generation in the region slows to a trickle in adulthood.
“This inverse relationship between the levels of neurogenesis and the
ability to form a long-term memory got us thinking that maybe one is due
to the other,” said Josselyn.
Running is known to boost neurogenesis in mice. So, to test whether
neurogenesis might impair memory, Josselyn and Frankland first taught
mice to fear a particular environment—the researchers placed the animals
in a distinctive box and gave them electric shocks—and then provided
them with access to a running wheel or let them remain sedentary. When
the mice were returned to the box after a day or a week, both groups of
animals tended to recognize the now-familiar environment and freeze—a
fear response. But if the mice were returned to the box after two weeks
or more, only the sedentary mice froze. The exercisers seemed to have
forgotten their fears.
Running imposes physiological changes aside from neurogenesis, of
course, but the team saw the same failure in memory recall when they
specifically increased neurogenesis pharmacologically in the mice. They
also found that inhibiting neurogenesis in exercising mice and in infant
mice made the animals better at remembering.
The team also showed that rodents such as guinea pigs, which have
reduced neurogenesis in infancy compared with mice, tended to remember a
fearful experience for much longer than did infant mice. And boosting
the guinea pigs’ neurogenesis caused them to forget their fears more
readily.
As Insel pointed out, previous studies have indicated that neurogenesis
in adults is beneficial to learning and memory—a finding that seems at
odds with Josselyn and Frankland’s. However, said René Hen,
a professor at the Kavli Institute for Brain Science at Columbia
University in New York, “previous findings have mostly been dealing with
the role of neurogenesis in encoding novel information”—that is,
learning and remembering something new. “Now, in the Frankland study,
they are looking not at the ability of encoding novel information, but
at forgetting older information. So one way to reconcile the two is to
think of it as a trade-off: if you get better at acquiring new stuff it
maybe at the detriment of keeping old stuff.”
Should the results of this study on rodents cause people to worry that
training for a marathon might make them forgetful? “People do always say
that running clears your mind,” said Josselyn, “and in a sense I would
say that’s true.” But clearing one’s mind is not necessarily
detrimental, she added. “For instance, I don’t want to remember where I
parked my car two weeks ago because that’s going to interfere with me
remembering where I parked it today. . . . We think that neurogenesis
and forgetting is an important part of healthy memory. We don’t want to
remember absolutely everything.”
K. G. Akers et al., “Hippocampal neurogenesis regulates forgetting during adulthood and infancy,” Science, 344:598-602, 2014.
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