Blowing up the brain

Baby-diaper chemistry offers scientists a better view of our brains’ wiring

Enlarging a sample of a mouse brain gave MIT scientists a detailed view of cells important to memory and navigation. 

F. Chen, P. Tillberg and E. Boyden/MIT

Blowing up a photo can show its details better. In the same way, enlarging a sample of brain tissue can help reveal the bigger picture of how cells in our brains are wired. A chemical similar to one found in baby diapers now gives scientists a new way to do just that.

For many years, disposable baby diapers have contained crystals nestled in their soft lining. Those crystals are a type of “super slurper” chemical known as sodium polyacrylate. It’s a polymer, or molecule made from long chains (hence the poly in its name). Decades ago, chemists learned that when these super-absorbers make contact with water, they suck up the liquid. Suddenly, what had been a powder made from crystals becomes a big gob of moist gel.

Over the years, chemists have turned super slurpers loose to tackle a host of problems beyond leaky diapers. For example, they can help pick up hazardous chemicals after a terrorist attack. But until now, nobody imagined their use in viewing the brain.

Credit that to a team of scientists at the Massachusetts Institute of Technology in Cambridge. They harnessed super slurpers for what they’re calling “expansion microscopy.”

It’s a bit like drawing a picture on a balloon’s surface, explains Edward Boyden, a neuroscientist at MIT. Blowing up the balloon makes the drawing bigger. “That’s what we were trying to do, but with a three-dimensional object like the brain.” By attaching the super slurper to molecules throughout brain cells and then adding water, the Boyden’s team can enlarge a sample of tissue to about 100 times its original volume.Science published details of the team’s technique online on January 15.

How it works

Typically, microscopy uses light and lenses to make tiny features appear bigger. Here, the team took something tiny and looked for a way to make it swell up so that it would become physically bigger.

The team starts by soaking a piece of preserved brain tissue in a solution with lots of the super slurper’s building blocks. “Then we add a second chemical and these building blocks start to form into long chains called polymers.”

This polymer attaches itself to molecules throughout neurons — nerve cells — in the tissue sample. Before long, the tissue has “all these little thin wires of polymer that are winding their way through it,” Boyden explains. It’s like the tissue has become “embedded in a sponge almost.”

That polymer is similar to the super slurper in diapers. “When you add water, it swells. And the brain gets bigger,” Boyden says.

Think about the spots on the surface of a polka-dotted balloon. When the balloon is deflated, the dots appear close together. But as it inflates, those dots begin to move farther apart. So it is with brain cells. “All the molecules in the brain get pushed away from each other,” Boyden says. Although the cells break apart, the expanded brain still has all of the same proportions as the original tissue.

The process also expands the spaces between neurons, called synapses. Chemical messages shoot across those synapses.

While some neurons can be centimeters long, synapses are usually “nanoscale,” Boyden says. They’re 100 billionths of a meter long or less.

With the new method, though, the synapses expand. As a result, researchers can see at the same time both big features, such as neurons, and previously nanoscale things like synapses.

Many scientists want to see parts of the brain more clearly, says Zayra Millan. A neuroscientist at Johns Hopkins University in Baltimore, Md., she did not work on the new project. “Expansion microscopy, which enlarges and fixes the specimens, is a novel way to do this,” she says.

“In an enlarged specimen, where local and long-range circuits are labeled, we have better visual access to the details,” she told Science News for Students. The ability to trace nerve fibers along their routes could help scientists trying to understand the brain and how different traumas alter it, she notes.

The new technique also could be a big step forward in helping scientists map the brain, Boyden says. “We can actually follow these neurons and see how they wire up.”

Power Words

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axon  The long, tail-like extension of a neuron that conducts electrical signals away from the cell.

cell   The smallest structural and functional unit of an organism. Typically too small to see with the naked eye,it consists of watery fluid surrounded by a membrane or wall. Animals are made of anywhere from thousands to trillions of cells, depending on their size.

chemical      A substance formed from two or more atoms that unite (become bonded together) in a fixed proportion and structure. For example, water is a chemical made of two hydrogen atoms bonded to one oxygen atom. Its chemical symbol is H2O.

chemistry  The field of science that deals with the composition, structure and properties of substances and how they interact with one another. Chemists use this knowledge to study unfamiliar substances, to reproduce large quantities of useful substances or to design and create new and useful substances. (about compounds) The term is used to refer to the recipe of a compound, the way it’s produced or some of its properties.

crystal  A solid consisting of a symmetrical, ordered, three-dimensional arrangement of atoms or molecules. It’s the organized structure taken by most minerals. Apatite, for example, forms six-sided crystals. The mineral crystals that make up rock are usually too small to be seen with the unaided eye.

fix  (verb: in chemistry) To treat a material so that it won’t move or chemically change.

lens  (in physics) A transparent material that can either focus or spread out parallel rays of light as they pass through it.

microscope  An instrument used to view objects, like bacteria, or the single cells of plants or animals, that are too small to be visible to the unaided eye. Microscopy is the field of technology devoted to using microscopes.

molecule  An electrically neutral group of atoms that represents the smallest possible amount of a chemical compound. Molecules can be made of single types of atoms or of different types. For example, the oxygen in the air is made of two oxygen atoms (O2), but water is made of two hydrogen atoms and one oxygen atom (H2O).

nano-  A prefix indicating a billionth. In the metric system of measurements, it’s often used as an abbreviation to refer to objects that are a billionth of a meter long or in diameter.

neuron or nerve cell  Any of the impulse-conducting cells that make up the brain, spinal column and nervous system. These specialized cells transmit information to other neurons in the form of electrical signals.

neuroscience  Science that deals with the structure or function of the brain and other parts of the nervous system. Researchers in this field are known as neuroscientists.

polymer  Substances whose molecules are made of long chains of repeating groups of atoms. Manufactured polymers include nylon, polyvinyl chloride (better known as PVC) and many types of plastics. Natural polymers include rubber, silk and cellulose (found in plants and used to make paper, for example).

sodium polyacrylate   When dry, this chemical is a crystal. Upon contact with water, however, it quickly swells into a moist gel that can grow to become many hundreds of time its original size. This property quickly gave rise to its popular name: the super slurper. The best known use for this chemical is to soak up urine, creating relatively leak-proof disposable baby diapers.

synapse  The junction between neurons that transmits chemical and electrical signals.