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A memory isn’t stored in your brain in a neat little package, but is instead spread across a pattern of cells in different regions. What's more, understanding this process could open the door to better treatments for conditions like Alzheimer’s or PTSD.

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Sources:

Main source:
https://science.sciencemag.org/content/367/6473/eaaw4325

Other sources:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2776484/
https://n.neurology.org/content/64/12/2004
https://www.sciencedirect.com/science/article/pii/S1364661313002118
https://science.sciencemag.org/content/317/5842/1230
https://science.sciencemag.org/content/323/5920/1492
https://www.nature.com/articles/nature11028
https://science.sciencemag.org/content/341/6144/387
https://www.nature.com/articles/nature08637
[♪ INTRO].

When you want to remember where you left your keys, you will, hopefully, conjure up a sort of image or idea of where you last had them. While it may seem like that memory just magically appears in your mind’s eye, the truth is that memories are far more physical.

That means they have to live somewhere in your brain. But, like, where? Is there a shelf labeled “keys” right next to the one that says “that time I tripped and fell down during the school play”?

Well it’s definitely not that literal. But thanks to advances in neuroscience, we can finally pinpoint the actual location of a memory; at least if you’re a mouse. To find a memory, first you have to make one.

And it’s easy to do that, you just do something. Anything, just like, watch me do this! That’s in your brain now!

You’re stuck with it! Your brain will then pick a bunch of cells to store a memory of the thing you just experienced, and it will activate them all at the same time. But those cells aren’t all in the same place, because the parts in your brain specialize in different things.

Your brain will pick cells across regions to store all the different aspects of a memory. For example, neurons in the visual cortex will store what you were seeing, and the cells in your amygdala will store how you were feeling. That specific pattern of cells, all firing together, is what the memory is now, in all of its multisensory glory.

The word scientists use to talk about this physical trace of a memory in a brain, the pattern of cells that activate to recall a memory, is an engram. It’s the unique pattern of cells activating together across the brain that makes a memory. And these cells are actually changed by the learning experience.

They form stronger connections with each other than with other neurons and they develop more dendritic spines: protrusions that help neurons talk to each other. So how do you find an engram? Ideally, if you could watch neurons fire, you should see the same ones fire when the same memory is activated.

And we can do that in mice. In a 2007 study published in the journal Science, researchers taught a mouse to associate a mild foot shock with a sound. This is a pretty commonly used protocol for studying memory.

If you see the mouse tense up, you know it remembers a shock is coming. And don’t worry, it’s just, it’s like a little zap. The researchers used a special glowing protein to tag the neurons that fired as the mouse learned.

That let them monitor what neurons fired when the mouse heard the tone and remembered what was coming next. A few days later, when the researchers played the sound again, they saw the same neurons firing. Basically, they saw that memory.

Now the next question was whether altering the neurons in the engram would mess with the memory. Which would prove that those neurons were holding that memory, and could even lead to, like, memory editing. So in a 2009 study, also in Science, researchers infected an area of the mouse’s brain with a virus that increased both how readily those neurons would activate, and the number of those neuron-connecting dendritic spines.

The virus basically made this area full of “super-neurons,” which the researchers hoped would be very likely to be used for storing a memory. Then, the researchers once again taught a mouse to associate between a sound and a foot shock, and then, just as planned, the super-neurons were used to store that memory. But the virus also had a kill-switch, which the researchers activated after training.

Like a tiny viral assassin, it took out the super-neurons. When they played the sound again, the mouse didn’t freeze up. It seemed to have no idea that a shock was coming.

It appeared that killing those specific cells also killed the memory. In subsequent research, scientists were able to manipulate both real and false memories. In one 2012 study, the researchers used a technique called optogenetics, where, by shining a special light on a part of the brain primed with light-sensitive proteins, you can turn specific neurons on.

The researchers taught a mouse to associate a sound with a shock and then pumped the engram cells, where they knew that memory lived, full of this light-sensitive protein. When they turned on the light, the mouse acted like it had just heard the sound and expected a shock, even though there was no sound. And in a 2013 study published in Science, researchers moved a mouse from an old cage to a new cage, and trained it to fear that new cage with electric shocks.

Then, they used similar optogenetic techniques to make the mouse remember its old cage while it was in the new one. When they put the mouse back in its old cage, it still seemed frightened; it thought that was where the shock had happened. These findings might make it seem like neuroscientists are officially masters of memory, able to edit, implant, and delete memories at a whim.

But it is very early days here. We’re nowhere close to handheld memory wiping gadgets à la Men in Black. But, if manipulating engram cells can add, delete, and modify memories in predictable ways, that does mean engrams are a useful model for studying memory.

Memory is such a crucial part of our lives and our identities, and by better understanding how it works physically, we demystify it. That could open the door for better treatments for conditions like Alzheimer’s or post-traumatic stress disorder. So while we will probably never have zappers to remind us where our keys went, we are getting closer to understanding how our brains store the memories that make us, us.

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