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A day in the (neuroscience) life: Electron microscopy

Researchers on the EM team are viewing the brain in unprecedented detail

March 17, 2022
 min read
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Researchers on the EM team are viewing the brain in unprecedented detail
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Jenna Schardt spends her days dealing with beams of electrons. A researcher on the Allen Institute’s electron microscopy team, she and her colleagues capture the highest possible resolution pictures of neurons and other parts of the brain.

Two masked people in a high-tech laboratory with multiple computer monitors and scientific equipment
Nuno Maçarico da Costa, Ph.D. (left) and Jenna Schardt (right) in the Electron Microscopy lab at Allen Institute

When we drop in on Schardt, she and two other scientists on the EM team, Forrest Collman, Ph.D., and Nuno Maçarico da Costa, Ph.D., are in the preparation phase for a new project to map the brain at incredible detail. They’ve just switched on a special type of electron microscope and are watching images appear on the monitor.

Geologic survey software showing aerial imagery with geological features and analysis tools.
Electron microscopy image collection at Allen Institute

Electron microscopes work by bombarding their subject — in the case of this team’s work, really really thin slices of mouse brain — with concentrated beams of electrons instead of visible or fluorescent light used in other kinds of microscopes. Because the wavelength of an electron is so much shorter than the wavelength of light, electron microscopes can get much finer grain details than light microscopes, magnifying a single neuron up to millions of times.

Person in blue gloves and mask examining metallic laboratory equipment in clean room
Forrest Collman, Ph.D. preparing for experimentation in the electron microscopy lab at Allen Institute

This particular electron microscope has a special attachment known as a cold finger (sadly, not named after the Bond villain), a thin vacuum pump cooled by liquid nitrogen that slurps microscopic impurities out of the sample of brain tissue. As Collman carefully pours the liquid nitrogen into a special container on the machine, da Costa and Schardt monitor the microscope’s progress.

“One of the cool things about this microscope is how much detail you can get when you zoom in or out, like Google Earth,” Schardt says, showing us the clear images on the monitor as she rapidly increases the magnification from a view of 3 centimeters, where we can see the entire petri dish with brain slices contained, down to 3 nanometers, zooming in on a tiny part of a single cell. “So that was like the equivalent of viewing the Earth from the heights Blue Origin [Jeff Bezos’ rocket company] reaches down to sea level.”

Person viewing aerial map software showing property layout on desktop computer monitor
Nuno Maçarico da Costa, Ph.D. working in the electron microscopy lab at Allen Institute

They’re working out techniques for a project that hasn’t yet begun — to trace the long-range connections from different types of cells in the brain at very high resolution. This work will build off a recently completed 5-year project to map every detail present in a cubic millimeter of mouse brain. The new project will use the same volume of a mouse brain with a special added staining technique that allows the scientists to see which kinds of neurons far away from the cubic millimeter are sending connections to make contact with cells in the tiny piece.

Photos by Erik Dinnel, Senior Producer at the Allen Institute, and text by Rachel Tompa, Senior Editor at the Allen Institute. Get in touch at press@alleninstitute.org.  

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