Nora Young:

I'm Nora Young, and this time on Spark another in our occasional series being human Now. That's where we look at facets of human existence that we once took to be distinctly ours and how they're changing in today's technological moment. This time memory from Wendy, we learned how the brain creates and stores memory. Turns out though that technology allows us to actually see and during physical representations of memories in the brain, these are known as memory engrams to explain will lead a systems neuroscientist, enter Joshua Sariñana

Joshua Sariñana:

A memory engram is a set of cells in a circuit of the brain that holds information about your experiences of life. If you were to see an engram under a microscope, you would see cells that are various colors. So for example, you might see some cells that light up green after you train a laboratory mouse during an associative learning task. So afterward you would see a slice of a part of the brain, say for example, the hippocampus, and you'd see a beautiful image of multiple neurons lighting up and those cells would hold the information about the experience

Nora Young:

Memory. Engrams are stored in the brain within a network of connected neurons, which Joshua says can be made to glow using proteins found in jellyfish.

Joshua Sariñana:

If you've ever been say to Puerto Rico, you can see the waters at night. And those bioluminescent jellyfish are quite amazing to look at, or I should say bioluminescent in general.

Nora Young:

Earlier Wendy Suzuki explained why as Canadian neuroscientist Karim Nader put it, the very act of remembering can change our memories. Bringing back an old memory creates a critical window during which that memory can be erased or manipulated. Neuroscientists have done this by artificially activating memory and engram cells in lab animals and inserting new information.

Joshua Sariñana:

So you can identify the engram in a part of the brain called hippocampus. And in doing so, you can more or less implant an experience that occurred prior to, and then you can kind of trick the circuit to associate it with an experience that happened in the past, even though in the present moment that experience is not happening.

Nora Young:

But these are mice talking about using such techniques to experiment on the human brain is still not feasible. And these experiments are limited to the manipulation of a single associative memories such as a learned fear response.

Joshua Sariñana:

Memories are both distributed and localized to a certain extent, so you won't have the full fledged memory, but you'll certainly see a considerable aspect of what neurons are taking part of the learning experience. Or you can see which neurons are responsible for recalling the memory and you can actually inhibit these cells and perturb the memory itself or the learning experience. So you can get pretty refined all the way down to the single cell level and all the way up to the circuit level.

Nora Young:

I understand it's now possible to manipulate memories using this kind of technology optogenetics. How does that work?

Joshua Sariñana:

The way in which the experiments were done back in oh 2011, I believe, was by first infecting the laboratory mice with these light sensitive channels. So you limit the expression of these channels to part of the brain called the hippocampus, and even more specifically to sub regions of this brain. So when you do that, you are able to really manipulate super specific parts of this brain network involved in autobiographical memories or experiential memories. And so the way in which this experiment was set up is by placing that mouse into an environment, environment one, and you allow that light sensitive channel to express in that environment only. So now those neurons have learned that environment, so then you put that mouse into a second environment that's very different and you shine light on the neurons that had learned environment one. So as the light sensor channels are turned on for environment one, the animal more or less perceives or remembers the first environment, even though it's in the second environment. As it's in the second environment, it receives a mild foot shock and it actually will associate the shock to the first environment rather than the environment it is actually in. So in that sense, it has created an association to an experience that's actually not having in that moment. So it has created a false association to an experience that was in the past.

Nora Young:

Do you think this sheds any light on this aspect of human memory where it is either subjective, prone to change or even a memory of a trauma which can be triggered when we're not in the exact same situation, but something is triggering that memory for us?

Joshua Sariñana:

We have cues that remind us of stuff all the time, whether or not we're attending to it or if it's unconscious, they can be the environment you're in. So like a context, it could be a smell, it can be something that's visual, it can be something that's very discreet, so it doesn't have to be in a full blown environment. So yes, we can have triggers that come at us and then that can actually result in say, a traumatic episode. There are some experiments that look at how to reactivate those experiences and then kind of ameliorate them by reactivating circuits that deal with more or less pleasurable experiences or experiences that are counter to the negative experiences as a way to help alleviate the traumatic response. But that's at the circuit level of the brain.

Nora Young:

So we were talking a bit before about the possibility of manipulating memories using optogenetics. What about implanting false memories? Can you tell me a bit about how researchers go about doing this?

Joshua Sariñana:

There's a circuit manipulation of false memories, and then there's the psychological aspect. Elizabeth Loftus back in the nineties helped kind of kickstart this line of research and since then it's become pretty routinized regarding how to implant false memories in people through photographs and through personal narratives. So you can have participants come in through a controlled lab setting and it's kind of under the guise of having the participant being told, we just want to understand how memories are recalled. So we're just going to tell you three different experiences that your family member or perhaps a friend told us about. And just kind of elaborate on them. They'll say, okay, here's experience one, tell us a bit more about that. Here's experience two, tell us a bit more about that. And here's experience three, and let's say that one is the made up experience that they want to implant in the person.

So they draw attention to that experience and sometimes they'll provide doctored image, so a photograph that maybe a family member gave to them. And so a canonical study, there was one where a family member gave a picture of a father and a son, and they doctored it to put them into a hot air balloon. And they said, do you recall this experience? And the person will say no. And in order to implant that false memory, the person has to more or less accept the suggestion that it could have happened even if they reject the fact that it did happen at first. So if you say, look at the photo, did this happen? They’re like, no, I don't remember. Or maybe that was my brother, but yeah, I have no recollection. And then the experimenter might say, well, imagine what could have happened if it did. And that's where things really start to kind of happen because it's imagination that is kind of critical for incorporating information into our brain. So as we begin to explore or imagine possibilities, we can kind of suck in information into these networks. When this happens, people start to really elaborate and create these connections. That's when false memories can be incorporated and up to half of the participants can have a full-blown memory implanted or at least partially implanted.

Nora Young:

So one of the reasons we're looking at this topic today is we want to understand the role of technology in changing how we think about memory. So overall, how have technologies like optogenetics changed what we understand about the nature of memory?

Joshua Sariñana:

Well, a lot. It's been a huge revolution in, I think in neurosciences because prior to we could only kind of eavesdrop on the brain through kind of electrical activity. It didn't give us precise information about which neurons. It gave us precise information about the temporal resolution of activity and generally where we were recording from, but we couldn't see which neurons were doing what. And now we have a very precise understanding of the neurons in the circuit and where they're projecting to and what they're doing at a particular time. And we can control those circuits now. So in turning on or off those circuits, we can have a much greater understanding about how the circuit is either taking part of the memory process or at least contributing to the larger functionality of the brain. And on top of that, it gives us insight into potential therapeutics of when these circuits malfunction.

Nora Young:

Yeah. Are there ways that this technology could be used to improve memory impairments or even diseases like Alzheimer's?

Joshua Sariñana:

Yeah, so there's some evidence for that. There's some research looking at how do we access information that we've forgotten and do memories we have forgotten, do they actually go away or are they still there? Is it a problem with access? So some research, suggest yes, it is a problem of access. So the information may actually be there. It's just that the connections between neurons called synapses may have just actually withered away in some capacity. And that if you can artificially activate them, say through optogenetics, that the memory is actually accessible, you just need to have the circuit activated in some artificial way. And with regard to Alzheimer's disease, we know that there's a type cells called microglia. And in Alzheimer's disease there is this interaction between inflammation and the over activation of microglia, and they kind of eat away at synapses. So essentially memory issues and those with Alzheimer's disease and not being able to access information. So there's some data suggesting that when you activate these circuits in these mouse models with Alzheimer's disease, you can actually help gain access to those memories that were essentially thought to be gone.

Nora Young:

And just finally, has all of this research changed the way you think about your own memories or the role of memory in your own life?

Joshua Sariñana:

One thing I noticed is that as a photographer, I go over my photos a lot and I didn't realize that it helped me a lot with my memories because I am constantly editing them, referring back to them. And for a while, I stopped my own photographic work because I was directing projects with other photographers, and that took its own type of work that took away from my own photography. And so I realized I was having trouble remembering events because I just didn't have access to those photographic cues, which contained information about what happened, where it happened, and what happened. So even though as much as I know about learning memory, it was just the experience of photographs and referring back to them, that actually surprised me.

Nora Young:

Joshua, thanks so much for your insights on this.

Joshua Sariñana:

Thanks so much, Nora. I really appreciate it.

Nora Young:

Joshua, Sariñana is a neuroscientist, photographer and writer exploring the connections between technology and art.