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Old 06-27-2012, 04:59 PM   #146
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Science's Long—and Successful—Search for Where Memory Lives

After more than a century of searching, an answer was recently found, strangely enough, just eight miles from Grauman’s. Although not located on any tourist map, the scene of the discovery can be reached easily from Hollywood Boulevard by heading west on Sunset to the campus of UCLA. There, amid one of the densest clusters of neuroscience research facilities in the world, stands the Gonda (Goldschmied) Neuroscience and Genetics Research Center. And sitting at a table in the building’s first-floor restaurant, the Café Synapse, is the neuroscientist who has come closer than anyone ever thought possible to finding the place where memories are written in the brain.

That spot, the physical substrate of a particular memory, has long been known in brain research as an engram. Decades of scientific dogma asserted that engrams exist only in vast webs of connections, not in a particular place but in distributed neural networks running widely through the brain. Yet a series of pioneering studies have demonstrated that it is possible to lure specific memories into particular neurons, at least in mice. If those neurons are killed or temporarily inactivated, the memories vanish. If the neurons are reactivated, the memories return. These same studies have also begun to explain how and why the brain allocates each memory to a particular group of cells and how it links them together and organizes them—the physical means by which the scent of a madeleine, the legendary confection that sparked Marcel Proust’s memory stream, leads to remembrance of things past.

“It’s amazing,” says neurobiologist Alcino Silva, codirector of the UCLA Integrative Center for Learning and Memory. “For the last hundred years, scientists have been looking for the engram in the brain. We have now gotten to the point that we know enough about memory and how memories are formed that we can actually find the engram, and by finding it, we can manipulate it.”

The implications of that finding hold promise for the treatment of human memory disorders. On the one hand, it points the way toward the selective targeting of neurons that hold memories of events so traumatic that people are disabled by them. That violent attack that you cannot get over? Deactivate those neurons in the amygdala that are linked to it, and you might still remember the attack but be freed from the unbearable pall of fear. With 3.5 percent of U.S. adults estimated to be suffering from post-traumatic stress disorder (PTSD) over the course of a given year, an effective new treatment would mark a mental-health milestone.

While PTSD sufferers remember too well, those with Alzheimer’s disease and other forms of dementia suffer the opposite problem. And just as Silva and others studying engrams have demonstrated the ability to delete memories, they have also shown they can strengthen them. This past July Silva’s colleague Sheena Josselyn, a neurobiologist at the University of Toronto’s Hospital for Sick Children, reported that her lab improved memory in mice bred to have the equivalent of Alzheimer’s. Using the same tools effective in creating and then purging fear, she boosted an entire brain region, the hippocampus, known to be critical for forming long-term memories.

Offering up what he concedes is a “science fiction kind of idea,” Silva wonders if physicians treating patients with Alzheimer’s “could direct memories to those regions of the brain that remain strong. Especially in neurodegenerative disorders, you have parts of the brain that are healthy and others that are not. If we find strategies to funnel memories to those parts that are still intact, we may be able to extend function longer.”

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