Has anyone ever approached you in a public place, perhaps the grocery store, and called you by name while you had no idea who they were? You may have struggled to place them, thinking they looked vaguely familiar. You may have tried to piece together the knowledge they knew about you. Where might you have met?
These sorts of memory failures involve context-dependent information, according to David M. Smith, Psychology. When someone you may have met once in the lobby of your office building suddenly approaches you in a different setting, your brain may have problems retrieving the correct memories that allow you to recognize that person.
“Everything you learn is linked to the place, the situation, where you learn it,” he explains. “The context becomes a really potent retrieval cue for your brain. The question is, why does it work that way? And how does the brain link a bit of information to the thing that triggers the memory?”
The Brain—Taking in New information, Storing It, and Retrieving It
Smith is interested in the biological mechanisms the brain uses to accomplish the cognitive function of memory. His lab, the Laboratory of Neurobiology of Learning and Memory, has used a series of experiments with rats to explore how the brain takes in new pieces of information, stores them, and then retrieves them later as needed.
“Our goal is to understand how memory works on a very basic level,” he says. “We hope that knowledge will turn out to be useful later to the understanding of memory failure, as in Alzheimer’s and other neurodegenerative diseases. You have to understand how the brain works normally to understand how it fails.”
Smith and his colleagues record neural activity in the brains of rats as they learn new behaviors, such as running through a maze, or remember a task learned earlier, such as which odor leads to a buried treat. “By tracking how neuron firing patterns in the brain change as the animal acquires new pieces of information, we can draw some conclusions about how the brain stores information about locations and odors and the memories of those things,” says Smith.
The Work of the Hippocampus—Spatial, Episodic, and Contextual Memory
Much of Smith’s research has focused on the hippocampus, a region of the brain long known to be concerned with memory. In particular, the hippocampus is involved in spatial memory (the location of things), episodic memory (the experience of events), and context memory (the linkage between a specific memory and a place or situation where it was learned).
“For every place you’re familiar with, the pattern in the hippocampus is different.”
“We’ve found that the hippocampus is specialized for generating complex and unique patterns of activity among many tens of thousands of neurons for every environment or context you ever encounter,” Smith says. “For every place you’re familiar with, the pattern in the hippocampus is different.”
To study this phenomenon, the researchers put rats in two very different environments: a black box and a white box. Monitoring each rat’s neural activity in its hippocampus, Smith and his colleagues saw one pattern when a rat was in the black box and a completely different one when they moved the same animal to the white box. “Then if you take that rat and put him in the black box again, the black box pattern will pop back, and vice versa,” Smith says.
In a further experiment with context, the researchers taught rats a set of odor problems where one odor in a pairing led to food reward and one did not. After the rats learned the rules of the game, the researchers changed them by introducing new scents and switching which of the original odors led to treats and which did not. Some of the rats learned the first set of odor rules in the black box and the second set in the white box. Others learned both sets of rules in the black box.
“Rats that learn both sets of conflicting rules in the same environment—the black box—have a lot of memory interference,” Smith says. “The rat remembers the first set of rules, and they keep intruding on his ability to learn the second set. But if the rat learns the second set of rules in the white box, which he’s never seen before, he learns them much faster because he’s in a new context.”
The Retrosplenial Cortex, Is It Where the Ability to Imagine the Future Resides?
Some of Smith’s most recent work, funded by a $1.6 million grant from the National Institutes of Health, focuses on the retrosplenial cortex—another area of the brain that also deals with memory. “The retrosplenial cortex and the hippocampus are connected by fiber pathways,” Smith explains. “The two regions talk to each other, probably a lot. Damage to either of these areas causes deterioration of navigation and spatial abilities.” Both of these regions are also among the first areas to show damage and cell loss in Alzheimer’s disease, which helps explain the tendency of Alzheimer’s patients to become lost or disoriented even in what should be familiar surroundings.
In one experiment designed to pinpoint the retrosplenial cortex’s function, Smith and his colleagues monitored the area in the brains of rats as they ran a maze. They found that the neurons in the retrosplenial cortex seemed to convey information about the rat’s location in the maze at any given moment. “We see the same overall pattern of neurons firing every time the rat goes through the maze,” Smith says. “But every spot on the maze has its own unique pattern associated with it.”
In another experiment, rats had to run a maze in a particular pattern, turning right or left at various choice points, in order to get food rewards. As a rat approached a choice point, the researchers observed neurons in its retrosplenial cortex firing in the same pattern they would normally fire when the rat had already reached the reward. “We think we’re seeing a simplified form of the ability to imagine the future,” Smith says. “The neurons are simulating what it will be like to be at the reward location.”
Smith’s interest in learning and memory dates back to his undergraduate work. “I was drawn to memory before I even knew there was a field of brain science about it,” he says. “I haven’t gotten bored with it partly because it’s still very mysterious. Trying to come up with the right kinds of experiments to answer questions about how the brain accomplishes memory is a fascinating, never-ending challenge.”