adulthood arrived, the visual systems of
mice with abnormal or missing perineuronal nets retained the ability to be
sculpted, Fawcett and colleagues have
found. These nets may hem in neurons
by calling in particular molecules, perhaps ones that stymie new nerve cell
connections, Fawcett and Difei Wang,
also at Cambridge, wrote in the July Cell
and Tissue Research.
Another impediment to malleability comes from a fatty substance called
myelin, which winds around neurons’
information-sending axons like insulation around an electrical wire, speeding
messages along. With this speed comes
less flexibility, as the myelin holds nerve
cell fibers in place. Wresting myelin off
of nerve cells restores plasticity in mice,
neuroscientist Takao Hensch at Boston
Children’s Hospital and colleagues have
shown.
Besides its physical constraints,
myelin also releases repressive signals.
One, a protein called ephrin-B3, holds
axons back, Stephen Strittmatter of
Yale School of Medicine and colleagues
reported in the March 27 Proceedings
of the National Academy of Sciences.
Removing ephrin-B3 allowed axons to
grow much more than those in normal
mice after an injury.
Other myelin-related proteins are
known to squash new nerve cell connections. One is the downer protein
NoGo. When a neuron detects NoGo, it
kicks off a series of changes that prevent
the growth of new connections. If NoGo
detector proteins are eliminated, nerve
cells become extra active and primed for
growth.
Already, results from various studies
have pushed scientists to stop talking
about cut-and-dry “critical” periods, but
rather, “sensitive” ones. The brain can be
coaxed into changing, even in adulthood.
Behavior revisited
While some researchers are overcoming physical barriers that swaddle nerve
cells and stunt new growth, others recognize an easier path to malleability:
manipulating nerve cell behavior to
make cells more or less likely to fire off
messages. “Changing the structure is
hard, but changing function is possible,”
says vision scientist Dennis Levi of the
University of California, Berkeley.
Rather than relocating the concrete
walls of a stone canal, the functional
approach alters the speed of water moving through that canal. One architecture
can sustain either a rushing stream or a
trickle.
Hensch and his colleagues started
with a hunt for substances in the brain
that were scarce during early life but
abundant as brain wiring windows
closed. The protein lynx1 popped out.
(Its molecular makeup resembles an
active molecule in snake venom.) Mice
genetically engineered to lack lynx1
spontaneously recover from early vision
problems, retaining a malleable brain
long into adulthood, Hensch and his
team reported in Science in 2010.
Normally, lynx1 puts a damper on
certain nerve cells’ excitability, a job
that helps the brain maintain the proper
flow rate of nerve cell activity. In a balancing act, the brain is poised between
too much activity (excited) and too little (inhibited). By muffling certain cells,
lynx1 holds the adult brain to a status
quo, called the excitatory/inhibitory
balance. But lose lynx1, and the brain
shifts toward a more excited, and more
malleable, state.
“You can pursue all of the molecules,”
Hensch says. “What’s exciting is that
they all converge on the excitatory/
inhibitory balance.”
A cartilage-like net (green) envelops a
nerve cell, restricting the formation of
new connections. Loosening the grip
could boost brain flexibility.
Neuroscientist Alessandro Sale of
the Institute of Neuroscience CNR in
Italy thinks that this balancing act may
explain many of his team’s results in
adult rats. Over the last several years,
Sale and colleagues have reported a
growing number of situations that can
repattern the adult rat’s visual system:
Exercise, living in a stimulating environment, starvation and even doses of
Prozac, which caused certain nerve cells
to become more active, all reinstated a
brain with more youthful behavior.
“At the very beginning, I was surprised
that many different noninvasive strategies were able to elicit plasticity in the
adult brain in such a powerful way,” Sale
says. But after looking closely, his team
believes that the procedures all alter the
flood of messages that nerve cells send.
Although many of these detailed
experiments in animals test the visual
system, the same general principles
might underlie other brain systems, Sale
says. Of course, the real goal of this work
is not to make blind rats see again, but to
help people retrain their brains.
Help for humans
Preliminary studies in people hint
that the excitatory/inhibitory balance is important for many aspects
of a healthy brain. People with Down
syndrome, Alzheimer’s disease and
even spinal cord injuries may have out-of-whack balances, studies suggest.
Though there’s no really good way to
see how nerve cells in a live human brain
behave, some training techniques (like
those used by Sale in rats) do appear to
resculpt the adult mind.
In some ways, the idea that experiences shape the brain is obvious to
anyone who has ever learned anything.
Playing the guitar, leisurely swinging
golf clubs and driving a taxi in London
for years all mold the adult brain, some
more dramatically than others. Just two
hours of playing a racing video game
changed the structure of volunteers’
brains, researchers reported in the
March 22 Neuron. Similar processes are
at the core of products that promise to
boost cognitive powers (though many of
