New brain mapping method links neuron to neuron across regions

Mature neuron

A team of researchers at Long Island, NY’s Cold Spring Harbor Laboratory have developed a brain mapping technique that can, in a single experiment, trace the paths of individual neurons like stepping stones from one to another.

MAPseq, which stands for multiplexed analysis of projections by sequencing, is different from the common “bulk tracing” method in that it can trace individual neurons. So instead of showing a number of regions connected to a source region, MAPseq should be able to give a specific reading that links one neuron to a single region of the brain.

How does it work? As published in the journal Neuron, Anthony Zador and his team injected a deactivated virus into the brain region they wished to study (in a mouse study). This virus had been engineered to contain individual RNA molecules, each with a different sequence. Like barcodes, no two are the same, and they would each become a marker for individual neurons.

Over time, these barcodes could be found in other regions of the brain, indicating they were connected to neurons in the first region. And the results are incredibly specific, showing a complex map of neurons, as opposed to a more simplistic map of regions.

The method’s inventor, Zador, uses an international airport as an analogy: “If you go to the international terminal, you see a long line of ticket counters,” he said. “If you want to go to Germany, it’s not enough to take any airline at the international terminal. If you stand in line at the counter for Air Chile, you’re probably not going to be able to buy a ticket for Germany. … You can print out a map showing all of the foreign countries that all of the airlines serve from your airport, but that doesn’t tell you anything at all about individual airlines and where they go. This is the difference between current labeling methods and MAPseq. The ‘individual airlines’ in my example are adjacent neurons in a part of the brain whose ‘routes’ we want to trace.”

Zador intends to study the brains of animals with developmental and psychiatric illnesses to find associations there in a much more detailed way than has been previously studied.

“Sequencing the RNA is a highly efficient, automated process, which makes MAPseq such a potentially radical tool,” said team member Justus Kebschull. “In addition to the speed and economy of RNA sequencing, it has the great advantage of making it possible for researchers to distinguish between individual neurons within the same region that project to different parts of the brain.”

- here's the Cold Spring Harbor article

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