Showing Some Spine: Imaging of nerve cell branches stirs debate

Two research groups have taken unprecedented, high-resolution images of nerve cells inside the brains of live mice–and come to seemingly contradictory views. Resolving their conflict about the stability of cell projections called dendritic spines could illuminate how the adult brain adapts to experience and stores information, say neuroscientists.

The research teams, which both report their work in the Dec. 19/26 Nature, studied different areas of the mouse cortex, the brain’s outer layer. The group led by Karel Svoboda, a Howard Hughes Medical Institute investigator at Cold Spring Harbor (N.Y.) Laboratory, examined a cortical region that processes sensory information from a mouse’s whiskers. The team led by Wen-Biao Gan of New York University School of Medicine investigated cortical cells that respond to visual information.

Both groups worked with mice genetically engineered to incorporate fluorescent proteins into the targeted nerve cells. Svoboda and his colleagues studied the green-glowing cells of their mice by implanting viewing windows in the rodents’ skull. Gan’s team instead thinned the skulls of their mice until they could image the nerve cells that glowed yellow.

Rafael Yuste of Columbia University, coauthor of a manual on imaging nerve cells, calls the experiments a “tour de force” that will set the stage for many similar studies in live animals.

Over days, weeks, and even months, the neuroscientists recorded images of the same rodent brains, focusing on the nerve cell branches known as dendrites. In particular, the groups studied each dendrite’s many stubby projections, or spines. Nerve cells communicate with each other through specialized junctions called synapses, and a dendritic spine provides the receiving end of a synapse, according to many neuroscientists.

In studies of 1-to-2-month-old mice, Svoboda and his colleagues found that although the dendrites of the mouse cortex remain stable, many of their spines quickly appear and vanish. The investigators report that about 50 percent of spines persist for more than a month, but the rest show up for only a few days or less. Trimming the whiskers of a mouse increases the percentage of spines that exist only briefly.

Svoboda’s team considers its data as evidence for a dynamic adult brain in which synapse-based circuits are constantly remodeled by the formation and elimination of dendritic spines, especially in response to new experiences.

Yuste, however, cautions that not every spine contains a synapse, and synapses don’t have to be on spines.

Gan’s group envisions a more stable adult brain. Even in their 1-month-old mice, more than 70 percent of dendritic spines persisted for more than a month. And in mice 4 to 10 months old, around 96 percent of spines were stable for at least a month, many of them enduring much longer.

Some spines “can even be maintained over the lifetime of an animal,” says Gan’s colleague Jaime Grutzendler. The researchers suggest that such long-term spines may offer a way for the brain to store information such as memories.

Grutzendler questions whether Svoboda’s team was really studying the adult brain because that group’s mice were all young. The different brain regions examined may also partly account for the two groups’ clashing data, he adds.

“The two papers are showing opposite results, something that doesn’t happen too often in science. It draws the skepticism of all the people in the field,” says a puzzled Yuste. “I find it hard to believe that one part of the cortex is very dynamic and the other is not.”

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