Columbia University Medical Center

Dopamine Helps Neurons Grow Up

Spiny projection neurons, like the one shown here, help the brain make decisions. A new study shows that the neurons mature with the help of dopamine.  Image: Ori Lieberman / Columbia University Irving Medical Center.

Adults select appropriate behavior with the help of the brain’s “spiny” neurons, and now a new study from Columbia neuroscientists shows how these neurons mature during childhood.

Why the study is important

In disorders like ADHD that arise during childhood, neuroscientists think these spiny neurons have not matured properly and cannot filter out extraneous information.

Background

Whether it’s deciding how to respond to an email or cross the street, the brain uses spiny projection neurons in the striatum to make a decision about how to respond.

Spiny projection neurons get their name from the multiple “spines” that sprout from the neuron’s many branches. The spines form synapses with other neurons to gather input from numerous parts of the brain.

When the balance of those inputs tell the neuron to fire, “the neuron is telling you to do something, like respond to a question, take a step forward, or take a bite out of an apple,” says David Sulzer, PhD, a neuroscientist at Columbia University Vagelos College of Physicians and Surgeons and the study’s senior investigator.

In babies, spiny neurons fire very easily and provoke appropriate–and inappropriate–actions. But with age and experience, the brain learns to distinguish between inputs that are important and those that are not important, and the spiny neurons mature and become harder to excite.

Spiny projection neurons are named for the numerous tiny spines located on the neurons’ many branches. Image: Ori Lieberman / Columbia University Irving Medical Center.

What’s new

The new study–conducted in mice­–shows that for the spiny neurons to mature, they must be exposed to dopamine during a certain window of time in development, equivalent to early childhood in people, around the time that attention deficit disorders begin to appear.

If the dopamine exposure occurs after this time period, the researchers found that the spiny neurons never mature.

What it means

If the spiny neurons never mature, inappropriate or immature decisions may result, along with an inability to focus.

“It’s possible that a lack of dopamine during adolescence and early adulthood could set up ADHD or other neurodevelopmental disorders,” says Ori Lieberman, an MD/PhD student at VP&S who conducted the research. “In that case, our findings may help point us in new therapeutic directions.”

It’s possible that a lack of dopamine during adolescence and early adulthood could set up ADHD or other neurodevelopmental disorders.

Attention deficit disorders are treated with drugs such as Adderall and Ritalin, which increase dopamine neurotransmission. The new study suggests that these drugs may be working to improve attention by affecting brain development during early childhood.

Why neuroscientists are intrigued

As a chemical messenger, dopamine is known to act in a matter of seconds to minutes. The new study is one of the first to show that dopamine can act over a period of days.

“That’s the exciting part for basic scientists,” Lieberman says. “It reveals a previously unknown role of dopamine in the brain.”

 

More Details

David Sulzer, PhD, is professor of neurobiology in the Departments of Psychiatry, Neurology, and Pharmacology at Columbia University Vagelos College of Physicians and Surgeons. He also is a NARSAD Brain & Behavior Distinguished Investigator.

The study, “Dopamine Triggers the Maturation of Striatal Spiny Projection Neuron Excitability during a Critical Period,” was published online in Neuron on July 26.

Other authors: Avery F. McGuirt, Eugene V. Mosharov, Irena Pigulevskiy, Benjamin D. Hobson, Sejoon Choi, Micah D. Frier, Emanuela Santini, and Anders Borgkvist (all at Columbia University Vagelos College of Physicians and Surgeons).

The work was supported by the National Institutes of Health (T32 GM007367, F30 MH114390, R01 DA007418R01 MH108186, R00 NS087112, and R01 NS075222) and by the Simons, Parkinson’s, and JPB foundations.