Method Provides 3-D Map Of Dopamine Signaling In The Brain

Functional magnetic resonance imaging (fMRI) usually provides a general picture of neural activity. A new method “gives molecular meaning to fMRI,” says Alan Jasanoff, a professor of biological engineering at MIT and leader of the team that developed the method. His team used a dopamine-sensitive MRI contrast agent to construct a three-dimensional map of the neurotransmitter in rat brains (Science 2014, DOI: 10.1126/science.1249380).

The contrast agent is a dopamine-binding variant of a paramagnetic heme protein. The researchers injected the protein into the nucleus accumbens region of rat brains. This region is thought to be involved with pleasure and addiction, both of which are linked to dopamine. They then electrically stimulated a nearby region of the brain to release dopamine.

They acquired fMRI images every eight seconds and averaged over multiple stimuli. The resulting 3-D dopamine map revealed that the highest levels were in the core of the nucleus accumbens. Electrochemical point measurements of dopamine release in identically treated rats revealed substantial dopamine release in the same regions identified by fMRI.

The fact that the fMRI measurements agreed with electrochemical point measurements is “comforting,” Jasanoff says. The fMRI method essentially allows the researchers to make many point measurements simultaneously. “From that, we get a map,” Jasanoff says.

R. Mark Wightman, an electrochemist and neuroscientist at the University of North Carolina, Chapel Hill, notes that the method’s sensitivity needs to greatly improve to get into the range necessary to detect endogenous dopamine levels. “What is exciting is the three-dimensional view—four when you include time,” he says.

The strategy should work for other neurotransmitters, Jasanoff says. “Developing other probes to produce contrast changes in response to different analytes will enable the technique to be extended, in many directions,” he says.

“It remains a bit down the road for us to apply these methods to study the human brain,” says Bruce R. Rosen, an fMRI expert at Harvard Medical School, “but it once again shows the power of MRI to surprise us with its flexibility and utility.”