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Rewriting Life

Hologram Method Used to Study Neurons

The approach could ultimately be used to rapidly screen new drugs designed to protect brain cells.

Scientists in Switzerland have developed a novel way to monitor a neuron’s electrical activity by bathing it in laser light. The technique, called holographic microscopy, doesn’t require the invasive electrodes or dyes typically used to measure cell activity. Researchers say the approach could be used to rapidly screen new drugs designed to protect brain cells.

Neuron in 3-D: Scientists can create three-dimensional images of neurons using a technique known as holographic microscopy.

Holographic microscopy shines laser light on an object and computationally reconstructs the object’s form based on how the light waves are deformed. The technology is most commonly used to study materials—to search for flaws on the surfaces of lenses or microchips, for example. But scientists have recently begun to use it on living cells.

Because cells are transparent, changes to the light that passes through the cell—known as the refractive index—can be used to calculate both the cell’s shape and its contents. The cell’s contents are directly related to its electrical activity: when a neuron becomes electrically active, channels in the neuron’s membrane open, allowing both water and ions to rush into the cell. 

“The change in water content changes the refractive index, so we are able to monitor current without electrodes,” says Pierre Magistretti, director of the Brain Mind Institute at the Ecole Polytechnique Fédérale de Lausanne, in Switzerland. Magistretti led the research. By using both conventional electrode recording and the holographic technique to monitor neurons grown in petri dishes, Magistretti and collaborators confirmed that holographic microscopy could accurately track electrical activity in the cell. The research was published this month in Journal of Neuroscience.

While electrode-based recording can monitor only a handful of neurons at a time, holographic microscopy could be used to monitor many more neurons simultaneously. In addition, the microscopes used in the technique can capture up to 500 images per second, generating movies of the cell’s electrical activity.

Magistretti says that beyond basic research, this approach could be used to quickly search for compounds with particular neural properties. During stroke, for example, neurons deprived of oxygen and glucose eventually die. The researchers showed that they can detect this type of cell death with holographic microscopy much more quickly than with other methods. For drug screens, they could re-create this stressful environment in a petri dish and then use holographic microscopy to look for compounds that prevent cell death.

Use of the technology is currently limited to a single layer of neurons grown in culture. The researchers now hope to use it to monitor simple neural circuits—connected neurons growing in a dish—as well as other cell types. The ultimate goal is to use it to monitor more complex configurations, such as slices of brain tissue, which better reflect the behavior of the intact brain. “If they can adapt the method to neurons connected in slices, it will be much more useful,” says Floyd Bloom, a neuroscientist at Scripps Research Institute. Bloom is optimistic: “I don’t think anyone could have predicted that they would have got as far as they did.”

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