New research explores the biology of forgetting

New research led by Quinn Pauli and Rob Bonin, associate professor, at the Leslie Dan Faculty of Pharmacy describes the biological processes involved in a key brain activity – forgetting.

“Forgetting is often thought of as an unwanted side effect of storing memories in the brain, but it can actually be a useful adaptation. Emotional and important memories tend to be stored for a long time, whereas less important memories are forgotten,” says Pauli, who will be graduating with a PhD in pharmaceutical sciences this spring.

“But this process can go wrong, for example when memories are too strong in post-traumatic stress disorder (PTSD) or there is too much forgetting in the case of dementia. Understanding the fundamental processes can allow us to understand when it goes awry.”

Pauli first learned about Bonin’s research program as an undergraduate, when she worked in his lab though U of T’s Undergraduate Summer Research Program. Bonin’s research focuses on nervous system plasticity or “rewiring” – how connections between nervous system cells can strengthen or weaken over time – and the molecular mechanisms of pathological pain. Pauli was interested in how pain and memory, two very different human experiences, could share some of the same molecular mechanisms.

“It’s amazing to me that these two different human experiences can have similar biological mechanisms,” she says. “I wanted to understand this better, and Dr. Bonin’s program had a unique way of approaching the study of memory and finding that overlap with pain.”

“Memories are so important to how we live. They shape who we are, how we think about the world, and how we interpret everything around us.”

After graduating in 2020, she began a PhD program in pharmaceutical sciences with Bonin as her supervisor.

Her PhD research applied the concept of plasticity Bonin’s group studies in the nervous system and chronic pain to study the brain and memories. Specifically, she focused on the biological mechanisms of forgetting by studying electrical activity in brain tissue from animal models. She was particularly interested in a cell surface receptor found in neurons called the NMDA receptor, which plays a key role in regulating the strength of connections between neurons, and thus the brain’s plasticity.

“Memories are so important to how we live. They shape who we are, how we think about the world, and how we interpret everything around us,” says Pauli. “I really wanted to understand how that abstract concept works at the biological level and what is actually happening in the brain to store and forget memories.”

Review article provides evidence for cell activity that allows forgetting

Pauli and Bonin recently published a review article in Neuroscience & Biobehavioral Reviews based on the background research for her PhD thesis that summarizes evidence for the processes the brain uses in remembering and forgetting.

Whereas memories can be created by strengthening connections between synapses on neurons or “potentiation,” a process called synaptic depotentiation weakens the connection between cells, leading to forgetting.

Pauli and Bonin found substantial evidence in the literature that neurons can adjust the strength of their connections during memory processes. They also summarized evidence that depotentiation is involved in forgetting and is regulated in different ways, which means there are different types of forgetting, some natural and others associated with a disease.

“If forgetting isn't a single process but several, then in principle we can target them separately,” says Bonin. “This framework opens a path to understanding various conditions such as PTSD and dementia, where these mechanistic differences can point toward new, effective treatments.”

Pauli combines research experience and interests to launch career in patient advocacy

On top her PhD research, Pauli participated in a variety of science communication initiatives during her time at the Leslie Dan Faculty of Pharmacy. This included organizing a national science communications workshop for graduate students, speaking directly with high school students about her research, and writing about chronic pain research for the broader U of T community.

She is now applying this passion for communicating science and her research background in her current career path.

After successfully defending her thesis late in 2025, she started a role as scientific director at CureGRIN Foundation, a patient advocacy organization for people with rare neurodevelopmental conditions called GRI Disorders. These disorders involve genes that code for the NMDA receptor, the same receptor she studied in her PhD research. Mutations in these genes can lead to symptoms such a developmental delay, intellectual disability, autism, speech delay and more.

As scientific director, she works with families, researchers, clinicians and industry to ensure GRI-related research is patient-centred and aligns with the needs and priorities of patients and families.

She says the learnings she gained during her PhD program have been invaluable in preparing her for this next step in her career.

“Practicing communicating science in different ways to different audiences and gaining an understanding of that responsibility and how to make science accessible was a huge learning throughout my PhD,” she says.

“It was always important to me to do something meaningful that aligns with my values, and this career path fulfills that. I’m so grateful to be able to apply my knowledge and skills to collaborate with others and make an impact.”