Lisbon, Portugal – In an exciting breakthrough, a recent study sheds light on how dopamine influences movement sequences, offering potential hope for the development of innovative therapies for Parkinson’s disease (PD). The research revealed that dopamine not only motivates movement but also controls the length and lateralization of actions, indicating a complex role beyond simple motivation.
Through pioneering experiments conducted with genetically modified mice, the researchers discovered that dopamine’s effect on movement is specific to one side, enhancing actions on the opposite side of the body where neurons are active. This finding highlights the potential for the development of targeted treatments for PD, focusing on the specific restoration of motor functions.
In PD, individuals experience a gradual loss of specific cells, known as dopamine neurons, which results in reduced strength and speed of movements. However, the study presents a critical aspect of movement affected by PD – the length of actions. People with PD may not only move more slowly but also take fewer steps in a walking sequence or bout before coming to a stop.
The study’s lead author, Marcelo Mendonça, points out that while dopamine is typically associated with reward and pleasure, it is the movement impairments that significantly impact the quality of life for dopamine-deficient individuals with PD. The concept of lateralization, or the asymmetric manifestation of symptoms in PD, led the research team to explore the theory that dopamine neurons not only motivate movement but also specifically enhance movements on the opposite side of the body.
To understand the brain’s activity during movement, the researchers developed a novel behavioral task that required freely-moving mice to use one paw at a time to press a lever in order to obtain a reward. Using a tiny, wearable microscope, the scientists were able to observe the activity of dopamine neurons in real-time in a dopamine-rich region of the brain known as the Substantia nigra pars compacta (SNc). This ground-breaking approach allowed them to observe how dopamine neurons reacted depending on which paw the mouse used.
One intriguing discovery was that the neurons excited by movement lit up more when the mouse used the paw opposite to the brain side being observed, indicating a side-specific influence of dopamine on movement. Additionally, the activity of these movement-related neurons appeared to encode the length of the movement sequences, providing new insights into the nuanced role of dopamine in the brain.
This research has the potential to revolutionize the approach to treating PD by uncovering the distinct roles of movement-related and reward-related dopamine neurons, opening up new possibilities for tailored PD treatments that address specific movement impairments. By understanding how dopamine affects movement at the cellular and molecular level, researchers aim to develop more effective and personalized therapies for individuals living with PD. The findings bring us one step closer to unlocking new therapeutic targets for enhancing motor function and improving the quality of life for those affected by PD.