The chemical messenger dopamine is an essential catalyst that fuels activities and behaviors ranging from movement to cognition and learning. However, neuroscientists have long debated whether these functions rely on rapid bursts of dopamine or on the neurochemical's slower action.
- By SHAFAQ ZIA
A new study led by researchers at Harvard Medical School provides an answer.
The work, conducted in mice and published Oct. 16 in Nature, shows that initiating movement doesn't require a rapid burst of dopamine but instead relies on slow activity of the chemical over time. By contrast, reward-oriented behaviors, related to motivation and learning, rely on fast dopamine action.
"If you read up on modern dopamine neuroscience, one conclusion from that body of literature is that dopamine may act as a fast neurotransmitter to trigger and modulate movement, yet our study shows that's not the case," said study senior author Pascal Kaeser, professor of neurobiology in the Blavatnik Institute at HMS.
The findings shed light on the molecular mechanism behind the drug levodopa (L-Dopa), widely used to treat Parkinson's disease. A hallmark of the condition is progressively diminishing dopamine, which over time leads to tremor and stiffness as well as a range of cognitive problems, including difficulty with memory, attention, thinking, and decision-making.
The study results help explain why L-Dopa generally improves the motor symptoms in Parkinson's, which do not require fast dopamine release, but is often worse for alleviating cognitive and memory problems, which tend to be under the control of fast dopamine signaling.
"Our work gets at the heart of the mechanism of L-Dopa action in movement. Our findings confirmed that L-Dopa enhances movement, but it does so without restoring rapid dynamics in the model we used," said study lead author Xintong Cai, a former HMS research fellow in neurobiology.
Dopamine signaling - fast and slow
Dopamine signaling is a complex, multistep process that involves a signal-producing neuron and various signal-receiving cells. It starts when a dopamine-producing neuron is activated by an electric impulse, which triggers the release of dopamine. Dopamine molecules move outside cells and bind to receptors on the surface of signal-receiving neurons. This binding initiates a cascade of signaling processes that regulate wide-ranging activities and behaviors, from movement and reward-seeking to motivation and learning.
