New Research Reveals How Neurons “Grab” Memories

Individual memories are encoded and stored by specific populations of neurons, known as engrams. SickKids

The brain’s ability to recreate former realities – otherwise known as memories – is one of its most impressive, enigmatic, and useful tricks. Even handier is the fact that, rather than simply remembering events as isolated snippets of history, the mind is able to organize its memories chronologically, so that memories of things that happened around the same time often become linked.

In a new paper appearing in the journal Science, researchers have discovered how specific populations of neurons become assigned to the task of encoding certain memories, revealing how events that occur within a particular timeframe are memorized by the same neurons.

It has long been accepted that individual memories are physically coded into the brain’s circuitry, with each being held by a specific collection of neurons called an engram. When the neural populations of two engrams overlap, these memories tend to become linked, while memories encoded by engrams that do not overlap are usually kept separate.

Previous research has suggested that the activity levels of neurons in a part of the brain called the lateral amygdala (LA) – which is associated with fear-related memories – tend to fluctuate periodically. Consequently, when we experience something frightening, whichever LA neurons happen to be the most active at that exact moment “grab” the memory, outcompeting their neighbors in order to create the engram. Yet this does not fully explain how separate memories that occur close together become linked.

To investigate, the researchers trained mice to develop two separate fear memories, each of which involved learning to associate a particular sound with an electric shock to the foot. Some of these mice were trained to develop a memory of the first tone six hours before being introduced to the second tone, while other mice were given a 24-hour break between forming the two memories.

The researchers then trained the mice to “forget” the second tone, by repeatedly playing it to them without giving them a shock, until the animals stopped freezing in fear when hearing the sound. Interestingly, those that had formed the two memories within six hours of each other appeared to also forget the first tone, while those that had had a larger interval did not. This led the study authors to conclude that memories formed within six hours of one another are encoded by the same neurons, which is why they become linked.

Image: The neurons of the amygdala encode fear-related memories. CLIPAREA l Custom media/Shutterstock

Next, the team injected the mice with a virus that would enable them to control the activity of their LA neurons using red and blue lights, in order to try and artificially link and unlink memories. To do this, they trained mice to memorize one tone, before waiting 24 hours to introduce them to the second tone. However, during the formation of this second memory, the researchers stimulated the same neurons that had encoded the engram for the first memory, ensuring they outcompeted their surrounding neurons and therefore grabbed this new memory.

When performing further behavioral tests, they discovered that the two memories had indeed become linked, despite occurring 24 hours apart.

The team then attempted to unlink memories by training mice to memorize the two tones six hours apart, but inhibiting the neurons that had encoded the first memory so that they would not be able to grab the second memory. Accordingly, their results showed that the memories were indeed unlinked, as extinguishing one did not automatically erase the other.

Knowing how memories become linked by overlapping groups of LA neurons could have major clinical significance, according to study co-author Paul Frankland, who explained in a statement that “understanding how memories are linked may provide hints as to how they become inappropriately connected in conditions such as schizophrenia.”

Understanding the neural circuitry behind overlapping memories could one day help to produce new treatments for cognitive disorders. deeepblue/Shutterstock

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