MRI with Genetic Reporter Builds Map of Brain Activity

MIT researchers have devised a way to monitor individual populations of neurons. It can reveal how the neurons interact with each other. The engineers used a new functional magnetic resonance imaging (fMRI) probe, based on an engineered enzyme delivered by a virus.

Functional MRI measures brain activity by detecting changes associated with blood flow.

"If we want to figure out how brain-wide networks of cells and brain-wide mechanisms function, we need something that can be detected deep in tissue and preferably across the entire brain at once," says senior Alan Jasanoff in a press release issued by MIT. "The way that we chose to do that in this study was to essentially hijack the molecular basis of fMRI itself."

A paper is published in Nature Neuroscience. In it, researchers describe a non-invasive imaging method that works across the brain.

The method is based on a probe (or “genetic reporter”) delivered by viruses. It codes for a protein that sends out a signal whenever the neuron is active.

Researchers called the protein NOSTIC (nitric oxide synthase for targeting image contrast). It's an engineered form of an enzyme, which is called nitric oxide synthase.

The NOSTIC protein can detect elevated calcium levels that arise during neural activity. It then generates nitric oxide, leading to an artificial fMRI signal that arises only from cells that contain NOSTIC.

The probe is delivered by a virus that is injected into a particular site. It then travels along axons of neurons that connect to that site. That way, the researchers can label every neural population that feeds into a particular location.

"When we use this virus to deliver our probe in this way, it causes the probe to be expressed in the cells that provide input to the location where we put the virus," explains Jasanoff. "Then, by performing functional imaging of those cells, we can start to measure what makes input to that region take place, or what types of input arrive at that region."

Experiments with laboratory rats allowed the researchers to determine which neural populations send input to the striatum. This is a brain region that is involved in planning movement and responding to reward. Input was monitored during or immediately following a rewarding stimulus.

The researchers hope to use the same approach to study other networks in the brain. And they aim to develop a broader perspective on how the brain works as an integrated whole.

"One of the things that's exciting about the approach that we're introducing is that you can imagine applying the same tool at many sites in the brain and piecing together a network of interlocking gears, which consist of these input and output relationships," concludes Jasanoff.

“With regular fMRI, we see the action of all the gears at once. But with our new technique, we can pick up individual gears that are defined by their relationship to the other gears, and that's critical for building up a picture of the mechanism of the brain."