Northwestern University researchers say they have identified the neurochemical signal likely missing in Parkinson’s disease. They reportedly discovered two distinctly different kinds of neurons that deliver dopamine to an important brain region responsible for both movement and learning/reward behavior.

“It has been dogma for decades that all dopamine neurons are somehow involved in both movement and reward, but this didn’t really make sense,” said Daniel A. Dombeck, Ph.D., the study’s senior author. “Now, it is so obvious in our recordings that there are different kinds of neurons. We can literally see this in behaving animals. Our findings will likely help answer many questions about Parkinson’s disease and other neurological mysteries.”

Dr. Dombeck, an assistant professor of neurobiology in the Weinberg College of Arts and Sciences of Northwestern University, conducted the study with postdoctoral fellow Mark W. Howe, Ph.D.

The findings provide a new framework for understanding the role of the dopamine system in movement control and learning/reward and how dysfunction of the dopamine system can result in a range of neurological disorders. Prior to this study (“Rapid Signaling in Distinct Dopaminergic Axons During Locomotion and Reward”), published in Nature, there was little evidence for rapid movement-locked dopamine signaling in the brain.

The scientists developed imaging techniques to see two distinct populations of dopamine neurons in the brain region of the striatum—one carrying signals for motor control and movement and the other transmitting signals about unpredicted reward. The findings overturn the current model of how dopamine neurons influence behavior, according to the researchers.

“There has always been this paradox about how dopamine does both movement and reward-based behavior,” Dr. Howe said. “What we found is that it does both and that there are different populations that do each one. And the neurons that do movement care about it on a very rapid timescale. These are the dynamics likely affected in Parkinson’s.”

The study could provide critical information for the development of more targeted treatments of Parkinson’s, a neurodegenerative disease caused by the death of dopamine neurons. Current therapies focus on replacing ambient pools of brain-wide dopamine. This study suggests that future treatments could be more effective by targeting the specific cell types, regions, and timescales that appear to be most involved in movement control.

Drs. Dombeck and Howe’s high-resolution imaging tools enabled them to observe the dynamics of the dopamine system in active mice. In studying the animals while either running on a wheel or receiving an unpredicted reward and imaging the axons of the dopamine neurons in the striatum during those activities, the scientists were able to tease apart different dopamine axons and identify the two distinct populations. They imaged a couple of axons to many dozens of axons at a time, depending on the experiment, to see what the activity looked like. The axons related to movement and Parkinson’s were active when the animal was running but not when the animal got a reward.

Also, using optogenetics, the researchers showed they can control an animal’s movement by shining a light on genetically labeled movement axons, showing that dopamine can trigger locomotion.

“This study changes the way we think about the role of dopamine neurons in movement,” said Raj Awatramani,  Ph.D., an associate professor in neurology at Northwestern University Feinberg School of Medicine, and who was not involved in the research.

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