New MERFISH Device Creates Unprecedented Atlas of the Human Brain

MERFISH, a new type of brain mapping sftware, helped Harvard scientists discover over 70 new types of neuron. | Image By DedMityay | Shutterstock

Using cutting-edge barcode imaging technology, Harvard neuroscientists mapped out 1 million brain cells and identified dozens of previously unknown neuron types.

Recently, researchers at the Princeton Neuroscience Institute called upon gamers worldwide to play a brain-mapping game.

Over the six years of the Eyewire game, a quarter million online gamers mapped more than 3,000 neurons and helped discover six new neuron types.

The Eyewire Museum exhibits one thousand of these neurons.

Now, in another breakthrough in brain cartography, Harvard University scientists have mapped over 1 million brain cells and discovered dozens of new types.

Read More: Citizen Science: How This Game Helps Map Your Brain

Cellular, Molecular, and Functional Atlas of the Brain

The human brain contains an average of around 100 billion nerve cells. In that scale, just a couple thousand neurons seem like a blip on the neural radar.

But thanks to advances in imaging techniques, neuroscientists are thoroughly mapping out neurons and continuously discovering new neural types.

Harvard’s Catherine Dulac and Xiaowei Zhuang led a research team to create a first-of-its-kind brain atlas. This atlas highlights not just the location, but also the molecular and functional profiles of over one million neurons.

The team also identified more than 70 new types of neurons.

The Harvard team’s map covers a tiny block of mice brain that’s just 2 by 2 by 0.6 millimeters.

“This give us a granular view of the cellular, molecular, and functional organization of the brain — nobody had combined those three views before,” said Catherine Dulac, the study’s co-senior author. “This work in itself is a breakthrough because we now understand several behaviors in ways that we never did before. But, it’s also a breakthrough because this technology can be used anywhere in the brain for any type of function.”

To create this neural atlas, the team used an advanced brain imaging technique called MERFISH.

MERFISH Creates an Atlas of Our Self

As described in the study published in Science, MERFISH, which stands for Multiplexed Error-Robust Fluorescence In-Situ Hybridization, can assign “barcodes” to cells. It can then read them out through imaging to determine the identity of individual RNA molecules.

According to Zhuang, the amazing property of the MERFISH method “is the exponential scaling between the number of genes that can be imaged and the number of imaging rounds. If you wanted to look at 10,000 genes, you could try the brute-force approach and do it one at a time, but of course, no one would ever try that. The MERFISH approach is very powerful because it allows us to image and distinguish thousands of different RNAs in just about 10 rounds of imaging.”

The significance of this brain map is that beyond just locating neurons, it provides their molecular profiles. Importantly, this means that researchers can now see how these neurons communicate with each other.

In addition, MERFISH’s very high sensitivity allows the identification of “lowly expressed genes that are critical to cell function.”

Will neuroscientists ever be able to map the entirety of the brain’s 100 billion neurons?

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