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Elly Nedivi
Picower Institute researcher and BCS assistant professor

How adaptable is the adult brain?

Two floors down from Matthew Wilson, Elly Nedivi is trying to understand how the brain stays flexible. Though the basic circuitry of the human brain is set during gestation and early life, the adult brain can still change: we can learn, remember, and react to new situations. “What we’re interested in is how the brain is able to constantly adapt,” says Nedivi.

In all likelihood, answering that question means explaining how the brain’s neurons subtly adjust synapses – the communication points where one cell meets another – to make connections weaker or stronger. To communicate, neurons generate electrical impulses; electrical activity, in turn, can cause physical changes in neurons. Several years ago, Nedivi’s lab found that creating electrical impulses in the brain rouses 360 different genes into action. This pool of genes, many of which had not previously been described, can offer clues to the brain’s adaptability, or what neuroscientists call “plasticity.”

So far, Nedivi’s research on just two of these “candidate plasticity genes” (CPGs) has shown that the brain can modulate cell communication on many levels. One gene, CPG2, causes the cell to withdraw receptors that respond to incoming signals, reducing its neighbors’ influence on it. Another gene, CPG15, encodes a chemical message that tells neighboring cells to grow and become more communicative. Now, Nedivi says, “we can go back and identify additional genes in [the CPG pool] that might be interesting in different ways” and study how all 360 genes might work together.

Nedivi has started using high-tech imaging to see how neurons adapt. Many of the genes her team identified were known to be involved in giving cells their shape and structure. But little was understood about what, if any, structural changes occur in adult brain cells. Nedivi teamed up with Peter So, an MIT professor of both mechanical and biological engineering, to devise a technique that literally provides a window into the adult mouse brain. The researchers implanted two glass discs a few millimeters in diameter into the scalps of living mice that had been engineered to express a fluorescent protein in some of their brain cells. The discs allowed the researchers to peer into the animals’ brains using a powerful microscope and, with the help of special software, to produce detailed, 3-D pictures of the cells. The team could see small but distinct changes over time, as the treelike branches of the cells grew and retracted.

With this tool, Nedivi says, “We can actually look at the neurons and see what they’re doing. And we can ask if they still do that if the brain is sick.” Nedivi envisions using her technique to look for structural defects in the brains of animals with diseases analogous to Alzheimer’s and Parkinson’s, as well as disorders thought to be caused by faulty synaptic communication, such as addiction and anxiety. And for the first time, researchers can view, in living brains, small-scale changes that are usually only studied in cultured cells. “ ‘Learning’ and ‘memory’ are general terms for something we can measure behaviorally,” Nedivi says. How this complex behavior emerges from tiny cellular events is one of neuro-science’s greatest puzzles.  – By Courtney Humphries, SM ‘04

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