05.2020 | THE SCIENTIST 43the Brain,” The Scientist, October 2018.) In other animals,
the researchers boosted neurogenesis after the mice learned
information thought to be stored, at least in the short term,
in the hippocampus. “When we did that, what we found was
quite surprising,” Frankland says. “We found a big reduction
in memory strength.”
His team was puzzled by the result. Adding to the confu-
sion, the researchers had observed a larger effect in memory
impairment with mice that learned, then exercised, than they
had seen in memory improvement when the mice ran first and
then learned. As he dug into the literature, Frankland realized
the effect was what other neuroscientists had called forgetting.
He found many theoretical papers based on computational mod-
eling that argued that as new neurons integrate into a circuit, the
patterns of connections in the circuit change, and if information
is stored in those patterns of connections, that information may
be lost. (See “Memory Munchers” on page 21.)
The notion surprised other neuroscientists, mainly because
up to that point they’d had two assumptions related to neuro-
genesis and forgetting. The first was that generating new neu-
rons in a normal animal should be good for memory. The sec-
ond was that forgetting was bad. The first assumption is still
true, Frankland says, but the second is not. “Many people think
of forgetting as some sort of failure in our memory systems,” he
explains. Ye t in healthy brains there’s tons of forgetting happen-
ing all of the time. “And, in fact, it’s important for memory func-
tion,” Frankland says. “It would actually be disadvantageous to
remember everything we do.”
Parylak says this idea of forgetting “certainly has provoked a
lot of discussion.” It’s unclear, for example, whether the mice in
Frankland’s experiments are forgetting, or if they are identifying
a repeat event as something novel. This is the point, she explains,
where doing neurogenesis research in humans would be benefi-
cial. “ You could ask a person if they’d actually forgotten or if they
are making some kind of extreme discrimination.”
Despite the questions regarding the results, Frankland and
his colleagues continued their work, testing mice’s forgetful-
ness with all types of memories, and more recently they asked
whether the forgetting effect jeopardized old and new memo-
ries alike. In experiments, his team gave mice a foot shock, then
boosted hippocampal neurogenesis (with exercise or a genetic
tweak to neural progenitor cells), and put the mice in the same
container they’d been shocked in. With another group of mice,
the researchers waited nearly a month after the foot shock before
boosting neurogenesis and putting the mice back in the con-
tainer. Boosting the number of new neurons, the team found,
only weakened the newly made memory, but not one that had
been around for a while.^11 “This makes a lot of sense,” Frankland
says. “A s our memories of everyday events gradually get consoli-
dated, they become less and less dependent on the hippocam-
pus,” and more dependent on another brain region: the cortex.
This suggests that remote memories are less sensitive to changes
in hippocampal neurogenesis levels.
The hippocampus tracks what’s happened to you, Frankland
says. “Much of that’s forgotten because much of it is inconsequen-
tial. But every now and then something interesting seems to hap-
pen,” and it’s these eventful memories that seem to get “backed
up” in other areas of the brain.Beyond memory
At NIMH, one of Cameron’s first studies looking at the effects
of neurogenesis tested the relationship between new neuro-
nal growth and stress. She uncovered the connection study-
ing mice that couldn’t make new neurons and recording how
they behaved in an open environment with food at the center.
Just like mice that could still make new neurons, the neuro-
genesis-deficient mice were hesitant to go get the food in the
open space, but eventually they did. However, when the animals
that couldn’t make new neurons were stressed before being put
into the open space, they were extremely cautious and anxious,
whereas normal mice didn’t behave any differently when stressed.Cameron realized that the generation of new neurons also
plays a role in the brain separate from the learning and memory
functions for which there was growing evidence. In her experi-
ments, “we were looking for memory effects and looked for quite
a while without finding anything and then stumbled onto this
stress effect,” she says.
The cells in the hippocampus are densely packed with rec-
eptors for stress hormones. One type of hormone in particular,
glucocorticoids, is thought to inhibit neurogenesis, and
decreased neurogenesis has been associated with depression
and anxiety behaviors in rodents. But there wasn’t a direct link
between the experience of stress and the development of these
behaviors. So Cameron and her colleagues set up an experiment
to test the connection.
When the team blocked neurogenesis in adult mice and
then restrained the animals to moderately stress them, their
elevated glucocorticoid levels were slow to recover compared
with mice that had normal neurogenesis. The stressed mice that
could not generate new neurons also acted oddly in behavioral
tests: they avoided food when put in a new environment,
became immobile and increasingly distressed when forced to
swim, and drank less sugary water than normal mice when it
was offered to them, suggesting they don’t work as hard as nor-
mal mice to experience pleasure.^12 Impaired adult neurogenesis,
the experiments showed, played a direct role in developing
symptoms of depression, Cameron says.Experiments have tied neurogenesis
to forget ting, anxiety, depression,
stress, and attention.