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Neurons generated in the adult brain
learn to respond to novel stimuli
MGH study finds first function for,
promising flexibility in adult-born nerve cells
BOSTON - November 15, 2005 - New brain cells that develop
in the olfactory system of adult mice appear to play a role in the
brain different from that of older neurons. The new olfactory neurons
are especially sensitive to novel stimuli, preferentially learning
to respond to new odors. This level of flexibility suggests that
such newly-generated neurons could be induced to adapt to and integrate
into other regions of the brain, perhaps allowing them to replace
neurons lost to injury or disease. The report from researchers at
the Massachusetts General Hospital (MGH)-Harvard Medical School
(HMS) Center
for Nervous System Repair (CNSR) appears in the Nov. 16 Journal
of Neuroscience.
"Our results show that these new neurons have a lot of plasticity
and can contribute to important learning and memory functions of
the brain, suggesting that similar, newly recruited neurons may
be able to function in other parts of the brain," says Sanjay
Magavi, PhD, who led the study as a fellow in the laboratory of
Jeffrey Macklis, MD, DHST, director of the MGH-HMS CNSR. "Eventually
we'd like to be able to redirect brain cell precursors or stem cells
to make other types of neurons in regions of the brain that do not
normally regenerate." Magavi is now a postdoctoral fellow at
Massachusetts Institute of Technology.
It had long been believed that neurons, the active cells of the
brain and nervous system, do not regenerate. Recent research has
shown, however, that new cells are added to certain areas of the
brain - including those involved with memory and the sense of smell
- well into adulthood. Very recent work, in particular a number
of studies from the MGH-HMS CNSR team, shows that neural precursors/stem
cells can be induced to form some of the much more complex neurons
in the cerebral cortex, the brain's highest-level structure. The
current study was designed to investigate whether newly generated
olfactory neurons simply replace older neurons or play a distinct
role in learning and memory.
The investigators used two groups of mice whose precursor cells
had been labeled to mark those that were dividing, allowing identification
of newly generated, adult-born neurons. These mice were then exposed
either to a panel of unusual odors or to a normal environment. Several
weeks later, the response of the adult-born neurons was evaluated
by measuring the activity of genes known to be expressed when olfactory
neurons respond to odors.
They found that the adult-born olfactory neurons of mice exposed
to the panel of odors subsequently responded more strongly to those
odors than did adult-born neurons of mice that had no experience
with the odors. The findings suggest that the new cells specialize
in detecting previously unencountered odors and in subsequently
responding to those smells.
"These contrasting responses suggest that adult-born olfactory
neurons have a unique role in the brain, becoming linked to new
smells while the older neurons essentially step out of the way.
And since adult-born neurons are continually being generated, there
is always a group of new cells waiting to link up with new stimuli,"
Macklis says. "We're also seeing how the environment can alter
adult-born neurons and how experience and activity are important
for making sure new cells integrate properly."
An associate professor of Surgery at Harvard Medical School, Macklis
also notes, "These results can contribute to our efforts, and
those of others in the field, to repair diseased brain and spinal
cord by directed development of specific neurons from precursor/stem
cells. Our experiments show that new neurons can join brain circuits
and function in complex ways - contributing to learning, memory
and potentially to motor function - and that we may need to retrain
the brain to use the new neurons effectively."
Along with Macklis, the study's principal investigator, the paper's
co-authors are Bartley Mitchell, PhD, Oscar Szentirmai, MD, and
Bob Carter, MD, PhD, all of the MGH-HMS CNSR. The work was supported
by grants from the National Institutes of Health, including a Jacob
Javits Investigator Award from the National Institute for Neurological
Disease and Stroke; the Leopold Schepp Foundation; the LifeBridge
Foundation; and the United Sydney Association.
Massachusetts General Hospital, established in 1811, is the original
and largest teaching hospital of Harvard Medical School. The MGH
conducts the largest hospital-based research program in the United
States, with an annual research budget of nearly $500 million and
major research centers in AIDS, cardiovascular research, cancer,
cutaneous biology, medical imaging, neurodegenerative disorders,
transplantation biology and photomedicine. In 1994, MGH and Brigham
and Women's Hospital joined to form Partners HealthCare System,
an integrated health care delivery system comprising the two academic
medical centers, specialty and community hospitals, a network of
physician groups, and nonacute and home health services.
Media Contact: Sue
McGreevey, MGH Public Affairs
Physician Referral Service: 1-800-388-4644
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