Can you have a memory without an experience?

Synapse #2: How smell might be the key to understanding memory

In Lois Lowry's The Giver, society gives up its collective memories of the sins and suffering of the world's past in order to establish a more ordered and supposedly happier society. Lowry's inspiration for The Giver actually stemmed from her visiting her aging father who was beginning to lose his own long-term memory. What she realized was that, without memory of it, there is no pain.

If one cannot remember a painful event, it might as well not have happened.

In The Giver, because the history of the human race had been erased from everyone's minds, not only did everyone forget the pains of the past, but they also could not engage in any of the activities which induced pain and suffering and this eliminated all nostalgia for the aspects of society that prevented unity and tranquility.

The Giver, I think, emphasizes a really interesting aspect of memory which is its profound influence in forming our identity. Are we not all fundamentally a collection of memories? This question is more interesting when one considers how constructive and fallible memory is. There are all kinds of documented cases of the fallibility of memory, especially regarding emotionally-charged events.

If memories are such a critical aspect of our self-identities, then I think it's an extremely interesting question to ask to what extent our memories can be manipulated not only by the nature of our experience but also via direct manipulation of the neurons in our brain.

In other words, can memories be created by neuronal events that solely take place in the brain?

What is memory?

I won't get into the details of the mechanism of memory formation here, but you should know that memory formation generally takes place in the hippocampus but involves other areas including the amygdala and cerebellum.

There is some debate as to the nature of the physical representation of memory, but one prominent idea is the engram theory of memory. The engram theory predicts that memories are stored as a group of neurons that are strongly connected and fire together when the memory is retrieved. After decades of searching for the engram, new imaging technology has more recently enabled scientists the ability to visualize and record the specific neurons that are involved in certain types of memory. For example, one study recorded the neurons involved in a contextual memory of a foot shock. Below is an example image with the neuron involved in the memory colored pink:

Given that scientists have been able to nail down specific neurons involved in memory formation, would it be possible to manipulate these neurons and create a memory of an event that never took place?

Memory formation in the absence of experience

To study whether a laboratory animal (in this case a rodent) has remembered something, scientists typically observe behaviors in response to stimuli such as lights, tones, etc. To look for evidence of a memory scientists might one day, for example, show a mouse a light and follow it with a mild foot shock. The next day, if the mouse responds to the same light by running away, we could infer that the mouse "remembered" yesterday's event where the light induced a foot-shock.

The problem with these stimuli, though, is that they are very complex. The visual system, for example, likely involves millions of neurons interacting in complex ways to recognize a light. It would, therefore, be an impossible task to try and manipulate these neurons to artificially create a memory of a light. What's the solution?

Enter the mouse smell center

Unlike vision, taste, or hearing, the organization of a mouse's smell center is actually relatively simple. For example, the neurons that recognize a particular smell actually converge on just a few clumps (called "ganglia") that can easily be visualized and manipulated. Below is an image of the neurons that respond to the smell of acetophenone:

A study in Nature Neuroscience from last year took advantage of this unique property of a mouse's smell center to try and artificially create a memory in a mouse simply by stimulating different neurons. In this case, evidence of a memory was recorded by observing a mouse’s reaction to a particular smell. One day, the researchers would pump a particular smell into a room in a chamber while at the same time electrifying the floor to induce a mild foot-shock. The next day, the same smell would be pumped into a room in the chamber, and if the mouse avoided that room, it would be reasonable to infer that the mouse remembered what happened yesterday.

Okay... so here's the cool part.

After learning which neurons are involved in the recognition of the smell of acetophenone, the researchers used mice who have never been exposed to acetophenone and used light to stimulate the neurons involved in the recognition of that smell and another area of the brain which is associated with fear.

Then, 24 hours later, the researchers pumped in the smell of acetophenone and despite having never experienced the smell of acetophenone, the mice avoided it. The authors of the study concluded that this is evidence of the mice remembering something without ever experiencing it.

Caveats

The results from this study, of course, come with a few caveats that ought to be discussed.

  • First, the researchers could not actually prove, of course, that the mouse "remembered" anything. They only used a mouse's response to a smell as a proxy for memory formation

  • I believe when people typically think of memory, they think of what is known as episodic memories, or memories of specific events that are often visual. The memory implanted in this study, however, is not of this nature. You know when you get a gut feeling that something is wrong around you but you don't know where it is coming from? That is what I imagine is happening in these mice, not distinct, strong memories.

  • This study used the fear center of the brain which may be more mailable than other areas. It would make sense evolutionarily for any organism, particularly mice, to have a default predisposition to "fear" something. It remains to be seen if one can also induce artificial memories in which a mouse prefers something. Have you ever had a gut feeling that everything is fine and dandy like you do when something is wrong? Me neither.

Why this matters to you

  • One of the many implications this study is that if we are able to artificially create memories via brain stimulation, then it stands to reason that we might be able to repair memories in people with amnesia or neurodegenerative memory disorders. Why it's unlikely that one could replace close to a lifetime of memories via brain stimulation, one could possibly accomplish a few important ones such as feelings of love and nostalgia for a now-forgotten child. One of the many sources of suffering for Alzheimer's patients and families is the experience of the diseased patient forgetting the name and identity of their children or other family and this research could be one small step to helping this case.

  • Besides neurodegenerative disorders, memory manipulation could be used as a tool for other kinds of therapies. For example, one study in Nature from 2015 found that activating positive memory engrams suppressed depression-like behavior in mice.

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🔗 Links, Links, Links

  • The Scientist put out a nice infographic and summary of the study I discussed in detail above. If you're more of a visual learner, I recommend you take a look.

  • If you want to know more about the technology used to manipulate mice brains in the study above, I highly recommend this Scientific American article on Optogenetics.

  • Researchers at Washington University in St. Louis have made progress on a blood marker for the detection of Alzheimer’s disease. A huge push in modern Alzheimer’s research is prevention because it might be the only way to stop this relentless disease in its tracks. Prevention requires early detection decades before symptoms and this research is a good step in that direction.

  • In case you’ve missed it, the USA is sending more stuff to Mars this week—this time including another rover and, for the first time, a helicopter named Ingenuity.

  • Related, don’t miss this fascinating article by the NY times about the logistics of bringing Mars rocks back to Earth. Spoiler: the process involves shooting a space soccer ball full of rocks into Mars orbit.

🎉 Celebrating Black in Neuro week!

This week was the first annual Black in Neuro week which celebrated Black neuroscientists all around the world. I wrote about this event last Friday and talked about why diversity is important in science, so check that out hereIf you click on just one link in this newsletter, let it be this one!

🖼 Image of the week

This week's image is an excellent picture of the organization of the hippocampus, one of the most important places of memory formation in the brain. Here, the hippocampus looks like a forest in the snow with the "snow" being the cell bodies of the neurons and the "trees" being the neuronal projections or axons. Notice the unique uniform organization of this area of the brain!

Image credit: Amandine Grimm

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