Nets full of holes catch long-term memories

CHICAGO —Tough, stable nets that swaddle nerve cells may be the ultimate memory catchers. These structures, called perineuronal nets, may store long-term memories, scientists reported October 19 at the annual meeting of the Society for Neuroscience.

“This is clearly a novel idea and it does, at first glance, look a bit way out,” says neuroscientist Eric Kandel of Columbia University. But there are good reasons to suspect that perineuronal nets hold memories, he says. “I am pleased to see this bold idea put out over the airways.”

The idea, presented by neuroscientist Sakina Palida of the University of California, San Diego, offers an explanation for how the brain can hold memories for decades. “Up to this point, we still don’t understand how we maintain memories in our brains for up to our entire lifetimes,” she says. A deeper understanding of how memories last may ultimately point to treatments for memory-stealing disorders like Alzheimer’s.

Synapses — connections between nerve cells — are known to hold memory information. But the proteins involved in this process are created and destroyed rapidly — a fluid situation that, like a game of telephone, could ultimately distort the memory. “The majority of these proteins turn over on the scale of a few hours to a few days,” Palida says.

But some of the sturdy proteins and carbohydrates that knit together to form perineuronal nets may last a lifetime.

Palida’s UCSD colleague Varda Lev-Ram fed mice food laced with a heavy form of nitrogen, allowing the researchers to study the life span of newly created net proteins. In some cases, the net proteins lasted for 180 days.

But these net components didn’t cover the entire nerve cell; they weren’t found at synapses. Other experiments revealed that newly formed synapses actually burn holes in the net, producing enzymes that chew through the net’s fibers. Like carvings in granite, the pattern of these holes stores memories, the team proposes. “The information is encoded in what is left behind,” Palida says.

Mice lacking a protein that punches holes in the net showed long-term memory problems, Lev-Ram, Palida and colleagues found. With a diminished ability to change their perineuronal nets, mice were worse at remembering a fearful signal.

The results focus on long-term memories, but it’s possible that perineuronal nets might also help hold memories over a shorter time scale, too, says neuroscientist Susumu Tonegawa of MIT. Perineuronal nets might provide support to nerve cell connections in the days after a memory is first formed.

Perineuronal nets swaddle nerve cells across the brain, the researchers found, not just in select areas, as previous experiments have suggested. Given this widespread pattern, the nets may have jobs beyond memory storage, Palida says. Other research suggests that these nets may lock nerve cells into place and prevent new connections, reducing the brain’s malleability; dissolving these nets in particular parts of the brain may be a way to enhance the brain’s ability to change, some scientists think (SN: 8/11/12, p. 18).

Young children’s nerve cells aren’t yet swaddled in perineuronal nets, other studies have suggested. As the brain matures, perineuronal nets begin to wrap nerve cells. The dearth of net coverage early in life may help explain why the first few years of life are a blur, a phenomenon called infantile amnesia, Palida says.