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Team sniffs out new info about brain cells

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New brain cells in the olfactory system are especially sensitive to novel stimuli, preferentially learning to respond to new odors, according to an MIT researcher and colleagues. 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 work is reported 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," said Sanjay Magavi, a postdoctoral fellow at MIT's Picower Institute for Learning and Memory. "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 led the study as a fellow in the laboratory of Dr. Jeffrey Macklis, director of the Massachusetts General Hospital (MGH)-Harvard Medical School (HMS) Center for Nervous System Repair (CNSR).

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, show that neural precursors/stem cells can be induced to form a few 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 said. "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 that "these results can contribute to our efforts, and those of others in the field, to repair the diseased brain and spinal cord using directed development of specific neurons from precursor/stem cells. These 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."

The work was supported by the National Institutes of Health, the Leopold Schepp Foundation, the LifeBridge Foundation and the United Sydney Association.

A version of this article appeared in MIT Tech Talk on December 7, 2005 (download PDF).

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