Branches of neurons in a mouse cortex
Image: Gao et al (Science, 2019)

It’s now possible to image an entire fly brain in just a few days, according to a new study—this might sound like a long time, but is in fact an incredible accomplishment, when you consider that the process would otherwise take weeks.

Brains aren’t easy to study—the human brain, for example, contains over 80 billion cells linked via 7,000 connections each, according to the new study published in Science. Even the far smaller fly brains are an incredible challenge to study comprehensively. The new research combines two microscopy methods to image and examine brains like never before.

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“It’s a new tool for trying to understand biological tissue, and not in a single cell context, but in a complete multi-cellular context at high resolution,” Eric Betzig, physicist and Nobel Laureate working at the Janelia Research Campus of the Howard Hughes Medical Institute, told Gizmodo.

The researchers combined two kinds of microscopy, called expansion microscopy and lattice light-sheet microscopy, in order to image the fly brain. Expansion microscopy involves first marking interesting features in a sample with fluorescing proteins, and then linking them with a polymer gel. An enzyme digests the tissue, and then the scientists add water, causing the polymer to grow and retain the shape marked by the fluorescing proteins. In this case, they grew the sample by four times.

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Expanding fly brain
Photo: Gao et al (Science 2019)

But imaging the expanded fly brain would require approximately 20 trillion voxels, or 3d pixels, which would take weeks for an electron microscope to image. The team decided to combine expansion microscopy with another imaging method, called light sheet microscopy. This uses thin, flat sheets of laser light and images the sample in flat sections, allowing for a faster process that also reduces background noise.

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Even Betzig didn’t think the method would work at first, he told Gizmodo, but when he viewed the results, he was “shocked” by the faithfulness of the expansion. Indeed, they were able to combine the methods to create high-resolution images, down to tens of nanometers, according to the paper.

But the research is nowhere near being able to create similar images of human brains, explained Betzig. They’re extending the method to (and have successfully imaged small pieces of) mouse brains, but a fly brain versus a mouse brain is the equivalent of “going from a mud hut to the Empire State Building,” he said.

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The researchers think they may soon be able to image multiple fly brains quickly and with incredible resolution. This is exciting, mainly because brains can vary by the individual, and comparing lots of brains could potentially teach us more about how these incredible feats of biology truly work.