New study finds dopamine neurons are more diverse than previously thought
In a new Northwestern University-led study, researchers identified and recorded from three genetic subtypes of dopamine neurons in the midbrain region of a mouse model.
Although there is a long-standing, common assumption that most — if not all — dopamine neurons solely respond to rewards or reward-predicting cues, the researchers instead discovered that one genetic subtype fires when the body moves. And, even more surprisingly, these neurons curiously do not respond to rewards at all.
Not only does this finding shed new light on the mysterious nature of the brain, it also opens new research directions for further understanding and potentially even treating Parkinson’s disease, which is characterized by the loss of dopamine neurons yet affects the motor system.
The study was published Aug. 3 in the journal Nature Neuroscience.
“When people think about dopamine, they likely think about reward signals,” said Northwestern’s Daniel Dombeck, who co-led the study. “But when the dopamine neurons die, people have trouble with movement. That’s what happens with Parkinson’s disease, and it’s been a confusing problem for the field.”
“We found a subtype that are motor signaling without any reward response, and they sit right where dopamine neurons first die in Parkinson’s disease. That’s just another hint and clue that seems to suggest that there’s some genetic subtype that’s more susceptible to degradation over time as people age.”
“This genetic subtype is correlated with acceleration,” added Northwestern’s Rajeshwar Awatramani, who co-led the study with Dombeck. “Whenever the mouse accelerated, we saw activity, but in contrast we did not see activity in response to a rewarding stimulus. This goes against the dogma of what most people think these neurons should be doing. Not all dopamine neurons respond to rewards. That’s a big change for the field. And now we found a signature for that dopamine neuron that does not show reward response.”
Dombeck is a professor of neurobiology at Northwestern’s Weinberg College of Arts and Sciences. Awatramani is the John Eccles Professor of Neurology at Northwestern University Feinberg School of Medicine. The paper’s first authors are Maite Azcorra and Zachary Gaertner, both graduate students in Dombeck’s and Awatramani’s laboratories.