Summary: New research sheds light on how dopamine affects movement patterns, offering promise for Parkinson’s disease (PD) treatments. Researchers found that dopamine not only stimulates movement, but also controls the length and distance of steps, different neurons for movement motivation and reward reception.
In new experiments involving genetically modified mice, the team found that dopamine’s effects on movement were lateralized, increasing actions on the opposite side of the body where the neurons are active.
These findings highlight the complex role of dopamine in movement and its potential to develop targeted therapies for PD, which focus on the restoration of specific motor functions.
Key facts:
- Dopamine and activity sequencesDopamine signals directly influence the length and initiation of movement sequences, suggesting a role beyond general motivation.
- Lateralization of dopamine effects: The study shows that dopamine’s effect on movement is opposite, which means that it improves the movement of the body, especially in the opposite part of the body where dopamine neurons are active.
- Potential for targeted PD therapiesUnderstanding the roles of movement-related and reward-related dopamine neurons opens new avenues for developing PD treatments that address specific movement disorders.
Source: Champalimaud for an unknown center
Visualize the act of walking. It’s something the most powerful people do without a second thought. But it’s actually a complex process involving different neurological and physiological systems. PD is a condition in which the brain gradually loses certain cells, called dopamine neurons, resulting in decreased strength and movement speed.
However, there is another important aspect that is affected: stride length. A person with PD may not only move slowly, but may take a few steps in a walking sequence or small steps before stopping.
This study shows that dopamine signals have a direct effect on the length of movement sequences, which takes us a step further to open up new therapeutic targets for improving motor function in PD.
“Dopamine is closely associated with reward and pleasure, and is a neurotransmitter often referred to as ‘feel good,'” pointed out Marcelo Mendonça, first author of the study. But for people with PD who are deficient in dopamine, it’s usually the movement disorders that have the biggest impact on their quality of life. One aspect that always interests us is the concept of lateralization.
“In PD, symptoms appear asymmetric, often starting on one side of the body versus the other. In this study, we want to explore the theory that dopamine cells do more than just motivate us to move, and specifically emphasize movements on the opposite side of our body.”
Shedding light on the brain
To this end, the researchers developed a new behavioral task that required free-moving mice to simultaneously press a paw to receive a reward (a drop of sugar). The researchers used single-photon imaging, similar to giving the mice a tiny wearable microscope, to understand what was happening in the brain during this task.
This microscope targets the Substantia nigra pars compacta (SNc), a deep dopamine-rich region of the brain that is most affected in PD, allowing scientists to observe the activity of brain cells in real time.
Using a special protein that glows under the microscope, they genetically engineered these mice so that their dopamine neurons light up when they move. This means that every time a mouse is about to move its leg or succeed in getting a reward, the scientists can see which neurons are firing and which are excited by the action or reward.
By looking at these glowing neurons, the findings were, quite literally, illuminating. “There were two types of dopamine neurons mixed in the brain,” Mendonca said. “Some neurons became active when the mouse was about to move, while others lit up when the mouse received the reward. But what caught our attention was how these neurons responded depending on which paw the mouse was using.”
How dopamine chooses sides
The team noticed that when the mouse used the paw on the opposite side of the brain, neurons excited by movement lit up more. For example, if you were looking at the right side of the brain, neurons were more active when the mouse used its left paw, and vice versa. The scientists dug deeper and found that the activity of these movement-related neurons not only indicated the initiation of movement, but also seemed to indicate or represent the length of the movement sequence (the number of lever presses).
Mendonca explains, “The closer the mouse is to the side of the brain where the mouse presses the handle, the more active the neurons become.” For example, when the mouse pressed the lever more often using its left paw, the neurons on the right became more excited.
But when the rat pressed the lever harder with its right paw, these neurons did not show the same increase in excitability. In other words, these neurons control not only the movement of the mouse, but also how much it moves and in which part of the body.
To study how the loss of dopamine affects movement, the researchers used a neurotoxin to selectively target dopamine-producing cells in the rat brain. This mechanism mimics conditions like PD, where dopamine levels decrease and movement becomes difficult. By doing this, they can see how much dopamine decreases the way rats press both paws.
They found that reducing dopamine on one side reduced lever presses in the contralateral palm, while the ipsilateral palm was unaffected. This provided further evidence for dopamine’s side-specific effect on movement.
Implications and future directions
Rui Costa, senior author of the study, led the story: “Our findings suggest that movement-related dopamine neurons do more than just provide the general impulse to move – for example, they can modulate the length of a sequence of movements in the contralateral limb.” . In contrast, the activity of reward-related dopamine neurons is more global, and does not favor one side over the other. This suggests a more complex role of dopamine neurons in activity than previously thought.
Costa reflects, “The different symptoms observed in PD patients may be related to which dopamine neurons are lost—for example, those more related to movement or reward. This may lead to disease management strategies tailored to the type of dopamine neurons that are lost, especially since we now know that there are genetically defined types of dopamine neurons in the brain.
So dopamine and neuroscience research news
Author: Heidi Young
Source: Champalimaud for an unknown center
Contact: Heidi Young – Champalimad for the unknown center
Image: Image credited to Neuroscience News.
Preliminary study: Open Access.
“Dopamine neuron activity indicates the length of the upcoming contralateral movement sequence” by Marcelo Mendonca et al Current biology
Draft
Dopamine neuron activity indicates the length of the upcoming contralateral movement sequence
Highlights
- He developed a free-motion task in which rats learned individual forelimb sequences.
- Activity-adjusted DANs indicate the length of contralateral activity sequences
- Activity of reward-modulated DANs is not lateralized.
- Dopamine depletion was contralateral, but not ipsilateral, in the length of the series
Summary
Dopaminergic neurons (DANs) in the substantia nigra compact pars (SNc) is associated with movement speed, and the loss of these neurons leads to bradykinesia in Parkinson’s disease (PD). However, other aspects of the strength of movement are affected by PD. For example, motion sequences are typically shorter.
However, the relationship between the activity of DANs and the length of activity sequences is unknown. We imaged the activity of SNc DANs in rats trained in a freely moving operant task, during individual forelimb sequences.
We found similar findings of SNc DANs increasing their activity before ipsilateral or contralateral sequences. However, the magnitude of this movement was higher for contralateral actions and was related to ipsilateral sequence length.
In contrast, the activity of reward-tuned DANs, which was largely distinguishable from that modulated by activity, was not lateralized. Finally, unilateral dopamine depletion impaired contralateral, but not epilateral, sequence length.
These results indicate that movement-evoked DANs are more than just a general motivational signal and that they promote aspects of contralateral movements.