A distinct subset of dopamine neurons, separate from the classic reward pathways, appears to influence movement in Parkinson’s disease. Researchers from the Champalimaud Foundation, a Portuguese biomedical research institution focused on neurology, oncology, and cardiology, reported these findings in Current Biology.
In their pursuit to understand how neuronal circuits shape movement, the team conducted experiments with laboratory mice. They developed a behavioral task in which freely moving rodents must press a lever with a paw to obtain a small reward, specifically a drop of fresh water.
To observe brain activity during this task, the scientists employed single-photon imaging. This technique provides a window into the brain’s structure, activity, and biochemistry. The focus was on the pars compacta region of the substantia nigra, a brain area deeply implicated in Parkinson’s disease pathology.
For visualization, dopamine neurons in the mice were genetically tagged to glow when active, using a fluorescent protein visible under a microscope. This approach enabled the team to pinpoint which neurons fired during movement and when a reward was received.
Across the data, two flavors of dopamine neurons were found intermingled within the compact substantia nigra. Some neurons activated as the mouse prepared to move, while others fired in response to the reward. An additional observation showed that neuronal firing patterns varied depending on which paw the mouse used to press the lever.
To explore how reduced dopamine affects movement, the researchers introduced a targeted neurotoxin to lower dopamine-producing cells on one side of the brain, simulating aspects of Parkinson’s disease. The resulting dopamine deficit on one side correlated with reduced paw pressing on the opposite side of the body, illustrating how unilateral dopamine loss can influence motor behavior.
These findings align with clinical observations that Parkinson’s symptoms frequently arise asymmetrically, with mobility on one side affected more than the other. The scientists emphasize that dopamine neurons have a more nuanced role in body function than previously thought. They are not solely tied to reward processing. The results pave the way for exploring treatments that selectively target specific dopamine neuron subtypes lost in the disease.
Earlier studies have also explored inflammation and autoimmune responses, suggesting new avenues for managing neurological conditions. This broader context underscores the ongoing effort to translate laboratory insights into therapies that improve movement and quality of life for people with Parkinson’s disease. [Citation: Current Biology; Champalimaud Foundation research team]