When brain waves fall out of sync, neurological diseases can develop—but understanding remains a challenge. A team at UHN’s Krembil Brain Institute (Krembil) has developed a mathematical model to reveal how different types of brain cells generate these essential rhythms.
A research team led by Dr. Frances Skinner, Krembil Emerita Scientist, and Dr. Jérémie Lefebvre, Krembil Affiliate Scientist from the Krembil Computational Neuroscience Hub, focused on theta-gamma rhythms—two types of brain waves that interact in the hippocampus, a brain region critical for memory. Using theoretical analysis and computer simulations, they examined how three distinct types of inhibitory brain cells work alongside excitatory ones to maintain these oscillating rhythms.
“Our models predicted specific cell interactions that help keep these rhythms stable,” says Dr. Skinner. “By understanding how these patterns emerge, we can explore how they change in neurological diseases and use them as potential targets for diagnosis and treatment.”
Because brain wave disruptions are linked to conditions like epilepsy and Alzheimer disease, the team’s findings could help guide the development of new treatments. “If we can pinpoint the specific cell types involved, we may be able to design therapies that restore normal brain function,” adds Dr. Lefebvre.Moving forward, these insights could pave the way for targeted treatments aimed at correcting disrupted brain rhythms in neurological disorders.
Spandan Sengupta, a Doctor of Philosophy candidate at the University of Toronto, and Dr. Afroditi Talidou, a Postdoctoral Researcher at the University of Calgary and a former Postdoctoral Researcher at Krembil Brain Institute, are first authors on this study.
Drs. Frances Skinner and Jérémie Lefebvre are the senior authors on this study. Dr. Skinner is an Emerita Scientist at UHN’s Krembil Brain Institute and an Adjunct Professor in the Department of Physiology at the University of Toronto. Dr. Lefebvre is an Affiliate Scientist at UHN’s Krembil Brain Institute, an Associate Professor in the Department of Biology at the University of Ottawa, and an Associate Professor in the Department of Mathematics at the University of Toronto.
This work was supported by the Natural Sciences and Engineering Research Council of Canada and UHN Foundation.
Sengupta S, Talidou A, Lefebvre J, Skinner FK. Cell-type-specific contributions to theta-gamma coupled rhythms in the hippocampus. Network Neuroscience. 2025 Mar 19;9(1):100–24. doi:10.1162/netn_a_00427.
This news story was originally written by UHN’s Krembil Research Institute.