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Living Well Study > Blog > Brain Health > New research challenges established models of Parkinson’s disease
Brain Health

New research challenges established models of Parkinson’s disease

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A new study led by researchers at McGill University is challenging a long-standing theory about how dopamine supports movement, offering insights that could reshape scientific thinking about treatments for Parkinson’s disease. By re-examining dopamine’s fundamental role in motor control, the findings suggest a more straightforward and potentially more effective way of understanding why current therapies work, and how future treatments might be designed.

Published in Nature Neuroscience, the research shows that dopamine does not directly determine the speed or force of individual movements, as has been widely assumed. Instead, it provides a crucial background condition that allows movement to occur at all. Rather than acting as a moment-by-moment controller of motion, dopamine functions more like a stabilising system that keeps the brain’s motor circuits ready and able to operate.

Senior author Nicolas Tritsch, an Assistant Professor in McGill’s Department of Psychiatry and a researcher at the Douglas Research Centre, explains that these results call for a fundamental rethink. According to Tritsch, restoring dopamine to a healthy baseline level may be sufficient to improve movement in people with Parkinson’s disease, without needing to recreate complex dopamine signals precisely. This reframing could simplify how researchers and clinicians approach treatment strategies.

Dopamine has long been associated with what scientists call motor vigour — the capacity to move with adequate speed, strength and fluidity. In Parkinson’s disease, dopamine-producing neurons gradually degenerate, leading to hallmark symptoms such as slowness of movement, tremors, stiffness and impaired balance. For decades, researchers have sought to understand precisely how dopamine loss translates into these motor difficulties.

The most common treatment, levodopa, is highly effective at improving movement, yet its precise mechanism has remained unclear. In recent years, sophisticated measurement techniques revealed brief, rapid bursts of dopamine release during movement. These discoveries led many scientists to conclude that such fast dopamine spikes directly control how vigorous each movement is. This interpretation has strongly influenced current theories of motor control.

The new study, however, points in a different direction. Tritsch likens dopamine’s role not to a throttle that sets movement speed, but to engine oil in a car. Without it, the system cannot function properly, but it does not dictate how fast the engine runs at any given moment. This analogy captures the idea that dopamine is essential for enabling movement, rather than fine-tuning each action as it unfolds.

To test this hypothesis, the researchers measured brain activity in mice as the animals pressed a weighted lever. Using a light-based technique, they were able to switch dopamine-producing neurons on or off with precise timing. If brief dopamine bursts were truly responsible for controlling movement vigour, altering dopamine levels at the moment of action should have changed how forcefully or quickly the mice moved. Instead, the researchers observed no such effect.

Further experiments with levodopa revealed that the drug improved movement by increasing the brain’s overall, or baseline, dopamine level rather than by restoring fast dopamine bursts. This finding provides a more straightforward explanation for why levodopa works so well, despite not precisely replicating natural dopamine signalling patterns.

The implications are significant. More than 110,000 Canadians currently live with Parkinson’s disease, and this number is expected to more than double by 2050 as the population ages. A better understanding of dopamine’s proper role opens the door to therapies focused on maintaining stable baseline dopamine levels. It also encourages a reassessment of older treatments, such as dopamine receptor agonists, which showed promise but caused side effects because they acted too broadly across the brain. With this new framework, scientists may be able to design more targeted and safer therapies in the future.

More information: Haixin Liu et al, Subsecond dopamine fluctuations do not specify the vigor of ongoing actions, Nature Genetics. DOI: 10.1038/s41593-025-02102-1

Journal information: Nature Genetics Provided by McGill University

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