Dopamine plays an unexpected role in movement and Parkinson's disease

Researchers at Northwestern University have uncovered a brand new understanding of dopamine, a crucial neurotransmitter traditionally associated with rewards. 

The new study, published in the journal Nature Neuroscience, reveals that dopamine’s role in the brain’s function is far more complex than previously thought.

Dopamine has been widely understood to be responsible for transmitting reward signals within the brain. This chemical is at the core of our feelings of pleasure and satisfaction that come from an enjoyable activity, and its dysfunction is involved in disorders such as addiction.

Surprising findings

However, the Northwestern University team has identified three genetic subtypes of dopamine neurons in the midbrain region of a mouse model. What they found was contrary to the long-standing assumption that dopamine neurons solely respond to rewards or reward-predicting cues.

Surprisingly, one genetic subtype of neurons was found to fire when the body moves, while displaying no response to rewards at all. 

“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 is motor signaling without any reward response, and they sit right where dopamine neurons first die in Parkinson’s disease.”

Study implications 

The implications of this discovery are substantial. Not only does it reveal new layers of complexity in the brain’s function, but it also opens new research directions for understanding and potentially treating Parkinson’s disease. 

Parkinson’s is characterized by the loss of dopamine neurons and is predominantly known to affect the motor system.

The new insights build on a previous study from Dombeck’s lab that found a population of dopamine neurons associated with movement in mice. 

“At the time, we thought it was just a tiny fraction of neurons,” said Dombeck. “And others continued to assume that all dopamine neurons were still reward neurons. Maybe some of them just had motor signals too.”

Focus of the study

To investigate, Dombeck collaborated with Rajeshwar Awatramani, who used genetic tools to isolate and label populations of neurons based on their gene expression. 

The experts tagged neurons in the brains of a genetically modified mouse model with fluorescent sensors, allowing them to visualize which neurons controlled different specific functions.

“This genetic subtype is correlated with acceleration,” said Awatramani. “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.”

What the researchers discovered 

In their experiments, about 30% of dopamine neurons glowed only when the mice moved, and these neurons were one of the genetic subtypes identified by Awatramani’s team. The other populations responded to aversive stimuli or rewards.

The Parkinson’s connection adds another layer to this complex picture. For decades, researchers have been puzzled by why Parkinson’s patients lose dopamine neurons yet have difficulties moving. 

This new study may provide a missing piece to this puzzle, revealing a potential connection between specific dopamine neurons and the motor symptoms observed in Parkinson’s disease.

“We’re wondering if it’s not just the loss of the motor-driving signal that’s leading to the disease – but the preservation of the anti-movement signal that’s active when animals decelerate,” said Dombeck. 

“It could be this signal imbalance that strengthens the signal to stop moving. That might explain some of the symptoms. It’s not just that patients with Parkinson’s can’t move. It could also be that they are being driven to stop moving.”

The research team acknowledges that their findings are just the beginning. “We’re still trying to figure out what this all means,” said Awatramani. “I would say this is a starting point. It’s a new way of thinking about the brain in Parkinson’s.”

More about dopamine 

Dopamine is a fascinating neurotransmitter with a myriad of roles. This chemical messenger transmits signals in the brain and other areas of the body. It plays several vital roles in both the central nervous system (CNS) and the peripheral nervous system (PNS).

Role in the brain

Reward and pleasure centers

Dopamine is best known for its role in the brain’s reward system. It’s associated with feelings of pleasure, satisfaction, and motivation. When you experience something rewarding (like eating your favorite food), dopamine levels increase.

Motor control

Dopamine is essential for coordinating smooth movements and regulating motor functions. This role becomes evident in conditions like Parkinson’s disease, where there’s a decline in dopamine-producing neurons, leading to motor symptoms.

Regulation of mood

Dopamine imbalances can influence mood and behavior. Low levels have been linked to feelings of apathy, lack of interest in life, and low motivation, and can be a characteristic of certain depressive disorders.

Role outside the brain

Digestion

Dopamine has a role in the digestive system, especially in the stomach’s motility.

Kidney function

In the kidneys, dopamine affects sodium and fluid balance.

Heart function

Dopamine can influence blood vessels’ width, affecting blood flow and blood pressure.

Disorders related to dopamine

Parkinson’s disease

This neurodegenerative disorder is caused by a loss of dopamine-producing neurons in the brain, leading to tremors, stiffness, and bradykinesia (slowness of movement).

Schizophrenia

Overactivity of dopamine transmission in certain brain regions might contribute to schizophrenia. Some antipsychotic drugs work by blocking dopamine receptors.

Addiction

Many addictive drugs increase dopamine neural signaling, leading to a temporary feeling of pleasure or euphoria. However, chronic use can lead to adaptations in the brain that decrease baseline signaling, potentially contributing to feelings of unhappiness or depression in drug abusers.

Depression

Some forms of depression are associated with reduced dopamine activity.

Natural ways to boost dopamine

Certain activities and lifestyle choices can naturally boost dopamine levels. These include a balanced diet, regular exercise, listening to music, meditating, and getting enough sleep.

While dopamine is often associated with pleasure and reward, its functions in the body are diverse and critical for various physiological processes. 

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