In the Brain, Memories Are Inextricably Tied to Place

A manmade virus that acts like “a remote control” for neurons helped psychologists research the connection.

Denis Balibouse/Reuters
It’s no coincidence that, when recalling a tragedy, we ask where someone was: “Where were you when President Kennedy was shot?”
Psychologists hypothesize that we lock in that memory by linking it to a where, that integrating many stimuli together helps us remember something particularly important. They call this process episodic memory formation: the locking of ideas and objects to a single place and time, to forming associations between different stimuli.
Using a a new process that involves an injected virus and a chemical “remote control for the brain,” psychologists are now a little closer to understanding it better.

Researchers at Dartmouth and the University of North Carolina announced Tuesday that new evidence indicates that the retrosplenial cortex—a little-studied region near the center of the brain—is important in the formation of this kind of information, called episodic memories. Specifically, they believe the retrosplenial cortex may help make sense of the burst of new stimuli in a new environment: It may be the place where the body’s senses are integrated.

When you walk into someone’s office, your brain records the location of the  pieces of furniture, screens, bookshelves and windows inside, said David Bucci, a professor of psychological and brain sciences at Dartmouth and one of the authors of the paper. Your brain may not remember the arrangement of that office if nothing important happens inside—in fact, you’ll probably forget it—but if something memorable does happen, you will commit the setup of that room to your memory. That room will be forever linked to what you learned inside it.

Researchers had known that a network of brain regions contributed to this function, but they weren’t sure how or what. Recent evidence had indicated the hippocampus was in fact less important in this process of immediate sense-making than earlier hypothesized, but researchers weren’t sure what other processes were at play. Bucci and his team now suggest that it's the retrosplenial cortex that dictates that immediate sense-making.

And they learned this with a specially engineered brain virus.

“It’s a remote control, if you will, of brain cells,” said Bucci. The process is called chemogenetics, and it has only recently become available to researchers. Using a very fine needle, researchers inject a region of a rat’s brain full of a synthetic virus. That virus then adds a line of DNA to nearby neurons, causing them to generate a receptor that essentially shuts down a cell briefly.

“There are plenty of naturally occurring receptors on brain cells,” Bucci told me. “This particular receptor connects to lots of machinery that cause [the cell] to go into silent mode. A part of the brain is turned off for two hours.”

It takes about a month for that receptor to populate the region of the rat’s brain. Then, researchers can inject the rat with a certain chemical that—though it travels throughout its body—activates only that receptor, temporarily shutting a region of the brain down. In this experiment, that meant researchers could shut down the retrosplenial cortex and watch as the test rats became incapable of linking the appearance of certain stimuli with getting fed. In other experiments, researchers have shut down feeding centers of the brain and memory cells. 

The ability, said Bucci, “to go in there and manipulate [a certain region of the brain] for a couple hours” was enormous.

Previous experiments on such centers, said Bucci, would “kill [those regions] permanently,” said Bucci. “And now the animal can’t eat.” Now that they’ve isolated the importance of shutting off the retrosplenial cortex, Bucci said scientists hope to figure out the importance of stimulating it using a similar technique.

Can they make rats better at learning—and, if so, what would be the implications of that?

Researchers also know little about how different regions in the memory-making process interact and communicate. And while Bucci stressed this experiment was “basic science”—meaning it was research for research’s sake and does not have a clinical objective—he said that the retrosplenial cortex was one of the first areas where evidence of Alzheimer’s appears, and understanding the process of episodic memory formation generally may help to make sense of the disease.

And chemogenetics—this fanciful technique that combines synthetic viruses and chemical brain control—is permitting experiments like this one that, half a decade ago, would have seemed impossible.