How the Brain Builds Memory Chains

Do you remember the first time you met your college classmate? You were probably nervous, talking a little too loudly and laughing a little too heartily. What else does that memory bring to mind? The lunch you shared later? The other classmates you met that night? Memories bring about memories, and as soon as you think of one, you think of more. Neuroscientists are starting to figure out why and how the brain builds memory chains.

It turns out that when two events happen in a short period, they feel somehow linked to each other. Researchers from the Hospital for Sick Children in Toronto (SickKids), the University of Toronto and Stanford University describe in this week’s Science that this apparent link has a physical manifestation in our brains. The experiments done by these three eminent universities are starting to scratch the surface of how memories are linked in the brain and, therefore, know that there’s a structure to our memory.

In the brains of lab mice, and in our brains, these structures are physically represented as clusters of neurons with strengthened connections to one another. These collections of connected cells are known as engrams (or memory traces) and they encode the memory of a particular event. Once that memory forms the set of neurons that make up the engram are more likely to fire. Furthermore, more excitable neurons—that is, brain cells that activate easily—are more likely to be recruited into an engram, so if you increase the excitability of particular neurons, you can preferentially include them in a new engram.

The question was, did that principle apply to two memories that happen close together in time? Neurons in a newly formed memory trace are subsequently more excitable than neighboring brain cells for a transient period of time. It follows then that a memory formed soon after the first might be encoded in an overlapping population of neurons, which is exactly what Frankland and study co-lead author Sheena Josselyn, found.

Josselyn, a neuroscientist at SickKids and the University of Toronto, and Frankland’s group was also able to tinker with the link between two memories by adjusting the excitability of neurons during different time points. In these types of experiments, they are only ever manipulating about 10 percent of the neurons in the amygdala. If this second memory cannot form, however, that implies something is changing in the other 90 percent of neurons. Their findings mean that neurons are competing to be included in the new engram, and in this competition excitability rules. That 10 percent of neurons are the winners because they inhibit the other 90 percent—it is winner take all.

Being able to look inside a brain at this level of specificity is wholly novel. It’s the kind of research that literally 10 years ago it would have been just bananas to think that we could go in and find these memories. The future of this research is to get a blueprint of how memory works.

Although the researchers could only look at two memories at a time, the ultimate goal is to understand a whole network of memories., and understand how memories layer on each other. What is knowledge, as opposed to what is a specific memory? To answer that question they must enter a largely brand-new territory. This study is only the second of its kind to date. Josselyn and Frankland studied overlapping memory formation in a brain region called the amygdala, associated with fear experience recollection. In a Nature article published in June neuroscientist, Alcino Silva at the University of California, Los Angeles, and his colleagues found the same principle to hold true in the hippocampus, which stores more factual knowledge.

The interaction between memories is, in fact, a fundamental part of how we form a coherent view of the world. That is a massive goal, but these experiments have pushed us in the right direction. These experiments are a stepping-stone toward understanding how we link information across time, and I think that’s one of the great mysteries of science because behind that is our ability to understand our world.


[1] Scientific American blog post written by Sara Chodosh (Scientific American Blogs).

[2] “Competition between engrams influences fear memory formation and recall”, A.J. Rashid, C. Yan, V. Mercaldo, H.L. Hsiang, S. Park, C.J. Cole, A. De Cristofaro, J. Yu, C. Ramakrishnan, S.Y. Lee, K. Deisseroth, P.W. Frankland, S.A. Josselyn. Science 22 Jul 2015, Vol. 353, Issue 6297, pp. 383-387. Available here.

[3] Feature Image is from MIT Magazine.




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