This Toronto researcher found where memories live. Can she help people with Alzheimer's and PTSD, too?

Everything was happening all at once. Stuck in a hospital room, Sheena Josselyn was fielding calls from reporters about a major breakthrough – proof that you could find and erase a memory. But first she had to give birth – and there were complications.

“I'm a scientist,” she recalls telling the anesthetist as she was wheeled in for an emergency C-section. “Actually, I have a paper coming out.”

She and her husband Paul Frankland, a fellow researcher, welcomed their daughter into the world on March 9, 2009 – just as their co-authored paper started making the rounds. It detailed how Josselyn, now a senior scientist at the Hospital for Sick Children and a University Professor at the University of Toronto, and her collaborators had successfully pinpointed where an individual memory lives in the brain and then proceeded to wipe it out.

Recalling that extraordinary day 17 years later, Josselyn is transported in time. The anxiety spikes her heart rate; she can smell the sharp antiseptic of the operating room. This is the strange alchemy of memory: our biographies, transcribed in biology. Memory, Josselyn says, is literally what makes us who we are – “the most fundamental part of being human.”

With appointments in psychology at the Faculty of Arts & Science and physiology at the Temerty Faculty of Medicine and Institute of Medical Science, Josselyn has spent the past 25 years trying to understand how memory functions and is now recognized as one of the most formidable minds in the field. She’s a fellow of the Royal Society of Canada and an elected member of the U.S. National Academy of Medicine. In 2025 alone, she received two major international prizes: the Peter Seeburg Integrative Neuroscience Prize and the Margolese National Brain Disorders Prize.

Her research explores how memories are encoded, stored and recalled – or, in the vein of sci-fi blockbusters, how they can be reprogrammed, implanted and erased. Her findings have furthered the understanding of everything from post-traumatic stress disorder (PTSD) to Alzheimer’s, a neurodegenerative disease that can rob people of their memories, selves, and ultimately, their lives. 

“We are beginning to solve how memory works,” Josselyn says. “This not only gives us incredible insights into what makes everybody uniquely human, but how to fix memory when it goes awry.”

Finding the engram

Where does memory live? It’s a puzzle that’s vexed scientists for generations.

One leading theory was the memories leave a physical trace in the brain – a cluster of neurons that scientists called an engram. But no one had ever found one. That is, until Josselyn came along. 

During her postdoctoral research at Yale University, Josselyn used viruses to shuttle memory-enhancing proteins into neurons in the brain’s fear centre. While only a small fraction of cells took it up, memory improved substantially. The simplest explanation was that memory wasn’t evenly distributed across the brain, but concentrated in a small, specific clusters.

But why those cells? The answer, Josselyn suspected, was competition. Neurons aren’t equally likely to capture an experience – they vie for it, with the most active cells at the moment of learning gaining a competitive edge. In other words, Josselyn’s protein-boosted neurons had a leg up. 

After founding her lab at SickKids in 2003, she put her theory to the test using the same viral technique to identify and destroy the cells she believed were storing a fear memory. It worked. The fear memory vanished leaving the others untouched – the first time anyone had deleted a single, specific memory. 

“That was a shift in the field,” she says of the paper that landed that hectic day in 2009. 

To probe these ideas further, Josselyn’s lab used a biological technique called optogenetics, drawing on algae’s light-sensitive proteins to develop an on-off switch for individual brain cells. This allowed Josselyn and her collaborators to activate or silence any neuron to, say, trigger a fear response in the absence of any threat, flip a memory from terrifying to safe – even implant an experience that never happened.

The problem of forgetting

Josselyn’s mother was a “rock” who, following her husband’s death, raised her and her two siblings by herself. She was the kind of woman who never missed a beat, Josselyn says. Then dementia set in. She died a few years later, though in many ways she was already gone.

“It’s horrible but amazing to watch these parts of her disappear,” Josselyn says. “She died, really, not as herself at all. She died as someone else.”

Losing her mom in such a painful, piecemeal process instills Josselyn with a sense of urgency about her work. She says she hopes that unravelling the brain’s machinery can lay the foundations for treating neurodegenerative diseases, although she’s clear-eyed about the distance that science must still travel.

“I’ve always said I want to contribute to our understanding of Alzheimer’s before I’m old enough to get it,” says Josselyn. “That was my joke, but now I’m getting up there.”

Memory problems aren’t always about forgetting, however. Sometimes, the brain remembers too well – or at least, too broadly.

In a 2025 paper in Cell, Josselyn’s lab explored a hallmark of PTSD: the way traumatic memories bleed beyond the inciting event to contaminate everyday life. Under stress, the brain encodes traumatic memories using far more neurons than usual, producing an oversized engram that gets triggered not only by the original threat, but anything that resembles it. 

The lab traced the mechanism to a cascade set off by cortisol – the stress hormone – which knocks out the cellular controls that typically keep an engram small and precise. Crucially, they also found a way to reverse it.

The breakthrough, however, raised difficult questions for Josselyn. While dulling or deleting a painful memory could help a patient with debilitating PTSD, bad memories are not always a malfunction, she notes. They’re how the brain learns. Beyond the individual, she argues, some memories – even extremely traumatic ones – carry a weight that belongs to all of us. 

“Memories of the Holocaust, the sort of collective memories of a society, have to be there," she says. “Or else we go on and make the same mistakes.”

The next memory makers

Josselyn has a long history with U of T. It’s where she earned her PhD in neuroscience and psychology, and where she met Frankland, a senior scientist at SickKids and a professor in the department of physiology and the Institute of Medical Science at Temerty Medicine and in the department of psychology in the Faculty of Arts & Science.

Although she left to pursue postdoctoral research in the U.S., Josselyn always knew U of T was where she wanted to land. It’s the kind of place, she says, where people swing for the fences.

She recognizes this intrepid curiosity in the students and postdoctoral researchers in her SickKids lab.

“I'm always amazed at how they bring so much of themselves and so much of their creativity,” she says. “My job is to nurture that.”

PhD candidate Sofiya Zbaranska, who studies social memory in the lab, says Josselyn gives her both the freedom to explore and the guidance that comes from decades of experience.

“We trainees bring creative ideas into the lab, and Sheena helps us refine them,” Zbaranska says.

Josselyn jokes that she’s long since run out of ideas, so she’s investing in the ingenuity of the next generation.

“They don’t really see limits,” she says. “They just see possibilities.”