CNS 2024 Q&A with Sheena Josselyn
For the past few decades, Sheena Josselyn has had a ringside seat to some remarkable technological advancements that have enabled scientists to study memories in ways once only imaginable through science fiction. Viral vectors, optogenetics, and live imaging have all enabled neuroscientists like Josselyn to explore how cells activate and interact to create specific memories in real time.
“We can literally watch a brain that’s thinking, that’s encoding a memory and then recalling it,” says Josselyn, a neuroscientist at the Hospital for Sick Children (SickKids) and University of Toronto. In her upcoming talk for the CNS annual meeting in Toronto, she will be detailing how use of these technologies in animal models is leading to new avenues for understanding memory circuits in people.
I spoke with Josselyn about her upcoming keynote lecture, how she became interested in neuroscience, and what excites her most about the memory research coming out of her lab.
CNS: How did you become interested in science?
Josselyn: I have always been interested in science, full stop. And I never quite understood what part of science I really liked. When I was doing my undergraduate degree, I thought I wanted to go to med school, because that’s what people who liked science seem to do.
One summer, I worked for my family doctor while his secretary was away for a couple of weeks. And at the end of that experience, I said to him, ‘you know, my job being your secretary was more exciting than yours, handling people’s coughs and colds.’ That’s when I realized being an MD was not right for me. I like puzzles, to feel challenged.
CNS: What drove you then to go into neuroscience?
Josselyn: In my fourth year of undergraduate, I took a class in neuropsychology. The professor taught us all about memory from the Larry Squire book. And I was fascinated; I thought it was the coolest thing that you could actually measure something in people and look at it animals, and how these basic fundamental things would come together and hopefully explain a lot of different things. So my path was a little bit tortured. I tried many, many things. But then I decided that I wanted to study memory and motivation in the lab, while also doing something clinically related outside of the lab, so I did a master’s degree in clinical psychology. I thought it was really fun, but I couldn’t really marry the two worlds so ultimately I settled on the lab work with rodents, moving here to the University of Toronto to concentrate on psychology and neuroscience.
CNS: What motivates your work with animal models?
Josselyn: I work with mice because it gives me incredible access to things that are going on in the brain, while you are teaching them and asking them to remember things. You can manipulate specific cells, genetically; you can manipulate them in real time using optogenetics. You can see what’s happened to that cell or that circuit of cells once you’ve trained an animal, once you’ve asked them to recall something, once you extinguish their memory, and once you’ve changed your memory. So you have incredibly powerful access to the brain. This is so important to understanding memory in people, as we can study different ways of looking at memory in people, but we can’t manipulate the brain in ways that are necessary to understand things pretty deeply.
CNS: In the abstract for your upcoming keynote address at CNS 2023, you discuss studying “engrams” in mice. How do you best like to explain engrams and how you measure them to non-specialists?
Josselyn: An engram is that bit of the brain that stores a memory.
An engram is a theoretical concept that’s been around for over 100 years. The thinking is that if there’s an experience, I must have some sort of trace of that experience in my brain, because I may need to recall it at some point. Nowadays, we think that a memory is stored in a bunch of cells that get together to form a circuit. And these cells are part of an “engram circuit,” with the engram storing the memory. So if we artificially turn these cells off in a mouse, it is as if the mouse has forgotten this memory. On the other hand, we can get the mouse to seemingly recall the memory if we turn these cells on. We’ve shown all these different ways of identifying these specific memory circuits in mice.
We are watching a memory unfold in real time. It feels like science fiction.
CNS: Is there a new line of work you are especially excited to present at CNS 2024?
Josselyn: Yes, I am going to talk about how neurons become part of an engram. While we’ve been doing these manipulation studies on memory in mice for many years, what we’re really excited about now is work where we just watch and see what happens. We use calcium indicators to tell us which cells are active and which ones are important in the memory. It’s very cool and something that I didn’t think we would ever be able to do in my scientific career. And now, it’s run by graduate students in my lab. We can predict based on a pattern of cells firing if they are going to be part of a particular engram, or not. We are watching a memory unfold in real time. It feels like science fiction.
CNS: How might this work be applicable in humans?
Josselyn: Although we cannot use the same techniques in humans that we do in mice, the work does show us that some memories are stored in these circuits, and that maybe we can develop tools, like smart drugs, to target just these cells. For example, if someone has PTSD, with an intrusive, troubling memory, that they have not been able to alleviate through other means, there could be a smart drug that just targets the active cells in that memory. So we would remind them of that memory and then give them a drug to affect those neurons that are activated. I can see something like that in the future, and it would derive from this basic, foundational work that my lab and many labs around the world have been contributing to.
CNS: What do you most want people to understand about this work?
Josselyn: For fellow neuroscientists: we understand a lot, but there’s still a lot we don’t understand about memories and how they’re formed. Typically, we look at one single memory and its retrieval, but we know that some memories can last for a very long time and some memories interact to create larger knowledge memories. There is still a disconnect between the neuroscience world and the cognitive world between the single memory studies and knowledge ones, and we need to start thinking more broadly.
For the general public: I think everyone has a basic interest in memories as they are what makes us who we are. We are some sort of weird sum total of our experiences and how we remember them. And we know that things can go wrong, especially in our aging population. So, the work we are doing in mice can help inform work to understand disorders like dementia and Alzheimer’s.
CNS: What are you most looking forward to about CNS 2024?
Josselyn: It’s always fun to welcome people to Toronto. I look forward to interacting with folks that aren’t necessarily neuroscientists, those who have a slightly different understanding or different take on psychology and memory. The sort of things that I study in the lab can be made much broader and richer by interacting with other people with a different perspective.
-Lisa M.P. Munoz