Teasing Apart Two Sets of Dopamine Neurons to Understand Parkinson’s

July 18,  2016

Researchers may have solved a long-standing puzzle about the brain cells that are lost in Parkinson’s disease (PD). The study, published in the July 11 online edition of Nature, finds that there are two distinct types of dopamine neurons lost in PD. Not only that, the study finds that each kind of neurons controls different types of behaviors, which could help scientist better target PD treatments.

Scientists have long known that the dopamine neurons lost in Parkinson's release dopamine for two different reasons — one, to help the body move and two, to respond to rewards. This is likely why Parkinson's medications sometimes both ease symptoms and lead to side effects related to compulsive behavior (the extra dopamine affects the brain’s reward system). But it's been difficult to explain how neurons are able to perform these two very different tasks.

To better understand how dopamine neurons work, Daniel A. Dombeck, Ph.D., and Mark W. Howe, Ph.D., at Northwestern University in Evanston, IL, developed sophisticated imaging techniques to watch them in action in the brains of laboratory mice. They used these tools to analyze dopamine signaling in brain cells as the mice rested, ran on a treadmill or received a reward of water.

Results

• The scientists identified two distinct populations of dopamine neurons in the striatum, a part of the brain associated with movement. The first type of neurons carry signals for control of the body’s movement and the other transmits signals about behavior in response to a surprise reward.
• The dopamine neurons related to PD movement were active when the animals were running but not when they got a reward. When researchers “turned on” specific dopamine neurons in the striatum, using a technique called optogenetics, this action caused mice to move.
• Surprisingly, they found that the dopamine neurons related to movement sent signals very rapidly and precisely timed to movement.
• The dopamine neurons related to movement were largely distinct from those related to reward. Each type sent its signals to different regions of the striatum.

What Does It Mean?

One of the major challenges of PD treatments is that they mainly focus on increasing overall levels of brain dopamine, rather than increasing levels based on the different pathways dopamine can take (movement versus reward). Because of this, treatment is often limited by side effects that are linked to excessive dopamine, such as hallucination or impulse control disorders.

This study has identified two distinct populations of dopamine neurons, finding that the activity of one group of dopamine neurons was precisely linked to motor activity. This changes scientific understanding of how dopamine signaling works, and may shed new light on how dopamine circuitry is disrupted in PD.

Not only that, it could help in the development of therapies. Current PD therapies aim to restore dopamine throughout the brain in a broad and untargeted fashion. The new study suggests that future treatments could be more effective by targeting the specific cell types, specific brain regions and recognizing that the timing of dopamine signaling appear to be most involved in movement control.

http://www.pdf.org/en/science_news/release/pr_1468855927