Alzheimer's disease / Memory / Neuroscience

How the brain remembers fearful experiences

Dr. Daoyun Ji drives to his lab every morning. If asked, he can easily recall the route he takes, “but, what are the brain signals at this moment when I hold this memory in my mind?”

In the Ji lab at Baylor College of Medicine, researchers are studying how neural circuits in the brain encode, consolidate, and retrieve memories. Understanding how the brain remembers can one day shed light on what went wrong when memory fails, such as it occurs in Alzheimer’s disease. Taking a step forward in that direction, researchers at Baylor and at Rice University have revealed for the first time the specific patterns of electrical activity in rat brains that are associated with specific memories, in this case a fearful experience.

Studying the workings of the brain in people is difficult, so scientists have turned to the laboratory rat. They have learned that when the animal is in a particular place, neurons in the hippocampus, appropriately called place cells, generate pulses of activity.

Specific patterns of brain activity help rats remember fearful experiences. Credit: the Ji lab.

“A number of place cells generates electrical activity called a ‘spiking pattern,’” said Ji, who is an associate professor of molecular and cellular biology at Baylor.  “When the rat is in a certain place, a group of neurons generates a specific pattern of spikes and when it moves to a different place, a different group of neurons generates another pattern of spikes. The patterns are very distinct. We can predict where the animal is by looking at its pattern of brain activity.”

Daoyun Ji, Ph.D.

But, are these spiking patterns involved in memory?

How to know what a rat is thinking

“Our laboratory rats cannot tell us what memory they are recalling at any particular time,” Ji said. “To overcome that, we designed an experiment that would allow us to know what was going on in the animal’s brain right before a certain event.”

In the experiment, conducted by first author Chun-Ting Wu, graduate researcher at the Ji lab, a rat walked along a track, back and forth. After a period of rest, the rat walked the same track again, but when the animal approached the end of the track, it received a mild shock. After it rested again, the rat was placed back on the track. This time, however, when it approached the end of the track where it had received the mild shock before, the rat stopped and turned around, avoiding crossing the fearful path.

“Before a rat walked the tracks the first time, we inserted tiny probes into its hippocampus to record the electrical signals generated by groups of active neurons,” Ji said. “By recording these brain signals while the animal walked the track for the first time we could examine the patterns that emerged in its brain – we could see what patterns were associated with each location on the track, including the location where the animal later got shocked.”

“Because the rat turns around and avoids stepping on the end of the track after the shocks, we can reasonably assume that the animal is thinking about the place where it got shocked at the precise moment that it stops walking and turns away,” Ji said. “Our observations confirmed this idea.”

When the researchers, in collaboration with co-author Dr. Caleb Kemere at Rice University, looked at the brain activity in place neurons at this moment, they found that the spiking patterns corresponding to the location in which the rat had received the shock re-emerged, even though this time the animal was only stopping and thinking about the location.

“Interestingly, from the brain activity we can tell that the animal was ‘mentally traveling’ from its current location to the shock place. These patterns corresponding to the shock place re-emerged right at the moment when a specific memory is remembered,” Ji said.

Future directions

The next goal of the researchers is to investigate whether the spiking pattern they identified is absolutely required for the animals to behave the way they did.

“If we disrupt the pattern, will the animal still avoid stepping into the zone it had learned to avoid?” Ji said. “We are also interested in determining how the spiking patterns of place neurons in the hippocampus can be used by other parts of the brain, such as those involved in making decisions.”

In addition, Ji and his colleagues want to determine whether this kind of mechanism is altered in animal models of Alzheimer’s disease. Some evidence shows that it is not that the animals don’t have a memory, but that somehow they cannot recall it. Using their system to read spiking patterns in the brains of animal models of the disease, the scientists hope to determine whether a specific spiking pattern exists during memory recall. If not, they will explore the possibility that damaged brain circuits are preventing the animal from recalling the memory and look at ways to allow the animal to recall the specific activity patterns, the memory, again.

Read the paper in Nature Neuroscience.

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Dr. Daniel Haggerty, a post-doctoral associate in the Ji lab, also contributed to this work.

This study was supported by grants from the National Institutes of Health (R01MH106552) and the Simons Foundation (#273886).

 

Ana María S. Rodríguez, Ph.D.

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