Old Brains Learn New Tricks

Imaging neurons in the living brains of mice shows that these cells can grow in surprising ways – perhaps suggesting new ways to treat spinal cord injuries and other neurological problems.

Scientists once thought the adult brain was set in its ways. Now they’re discovering that adult neurons have a remarkable ability to grow and change – and researchers at MIT have shown that some neurons can sprout new branches and retract old ones.

These findings, published in last week’s issue of PLoS Biology, an online journal from the Public Library of Science, add to a growing body of evidence that older brains are, in fact, still agile. The same method that researchers applied in the current study could be used to assess the best ways for encouraging brain cells to grow, which would help people with spinal cord injury, stroke, and other disorders. “This could be a powerful diagnostic or a way to test therapies,” says Elly Nedivi, the professor of neurobiology at MIT who led the research team.

Nedivi and her collaborators used mice that had a few neurons labeled with fluorescent dye, so the cells could be seen under a microscope. They shaved off a small piece of a mouse’s skull and covered the opening with glass. Using that “window,” they then took pictures of the fluorescent neurons with a two-photon microscope, a technique that provides very high-resolution images of living brain tissue. And, finally, to record how the neurons changed over time, they captured images of the same neurons over several weeks.

Their laborious work paid off. What they found was that dendrites – those treelike extensions on neurons which receive information from other brain cells – grew, shrank, and changed over time. “You see the full range of types of growth you see during development, such as growth spurts, new processes, or new branching from [the main neuronal process],” says Nedivi. “This is what the brain is doing on a day-to-day basis.”

In previous studies, scientists had observed structural changes in tiny spikes on the surface of dendrites, called spines. But, by painstakingly reconstructing larger portions of neurons, Nedivi and her colleagues Wei-Chung Lee, Peter So, and Hayden Huang revealed larger-scale changes in the dendrites, which may have gone unnoticed with other methods.

“We know that throughout life we learn things, so synapses must be changing in some way. But people didn’t know if the same synapses were getting stronger or weaker, or if whole new ones were forming or old ones were disconnected,” says Harvard neuroscientist Joshua Sanes, who generated the mice used in the MIT study. “This raises those last possibilities: that some changes may involve wholesale formation of new synapses or loss of old ones.”

Edward Callaway, a neuroscientist at the Salk Institute in San Diego, says these new findings are the first clear indication that larger structural changes occur in dendrites. But, he adds, researchers still need to show that these structural changes are linked to changes in the connections between neurons.

Nedivi and colleagues now plan to search for ways to boost the growth and plasticity of neurons, which could eventually provide a new approach to treating spinal cord injuries. They will also determine if such structural changes correlate with changes in learning and behavior, such as might occur after mice are challenged with a more stimulating environment or new tricks.

An additional area of interest, according to David Kleinfeld, a physicist who studies neurobiology at the University of California, San Diego, would be to investigate what happens to neurons in brain regions affected by stroke. “Blood vessels sprout in the ‘dead zone’ left after a stroke,” he explains, “but it’s unknown if you get sprouting of neurons at the same time.”

The MIT researchers will also look at mouse models of diseases such as Alzheimer’s, to figure out if neurons involved in such disorders grow too much, too little, or in the wrong way.

Image on home page courtesy of Elly Nedivi.

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