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Holograms can reveal brain's inner workings

Usually with imaging of the inner workings of the brain, we cannot get down as far as the individual neurons. Instead we rely on patterns of electrical activity across hundreds, or thousands of neurons – or we go by oxygen levels in the haemoglobin passing through the brain.

But, if we could image individual neurons during the firing process, it would add another tool into our toolkit for working out at a fine level, exactly how neurons are assigned into functions.

We might now have the first barest twinklings of that capability. A team of neurobiologists, psychiatrists, and advanced imaging specialists from Switzerland’s EPLF and CHUV report in The Journal of Neuroscience how Digital Holographic Microscopy (DHM) can now be used to observe neuronal activity in real-time and in three dimensions—with up to 50 times greater resolution than ever before.

Sadly, this is a microscope technique for working with neurons in Petri dishes. We' re not looking at imaging the neurons on the inside of your brain in this detail any time soon. However, even in a petri-dish, living neurons still bond together into active networks, and we can now use the dishes to discover in real-time, just what exactly is going on when they do this. In addition, because the technique is non-invasive, no dies or external electrical sources will invade the neurons' space, so there is no danger of contaminating the results.

Senior team member Pierre Marquet of EPFL’s Brain Mind Institute and a lead author of the paper stated: “DHM gives precious information not only about the shape of neurons, but also about their dynamics and activity, and the technique creates 3D navigable images and increases the precision from 500 nanometers in traditional microscopes to a scale of 10 nanometers.”

A simple explanation for DHM is to picture a rocky outcropping in a calm ocean, being passed by regular waves of exacting height, a precise distance apart. The waves strick the rocks and deform around them, flowing past the outcropping to a detector on the other side. This detector reads the shape of the waves, and is able to infer the shape and composition of the outcropping from how it distorted those waves.

This is how DHM works. DHM uses a single-wavelengrth laser beam, pointed at the object, passing through to a collector on the other side. At the same time, a second, identical beam passes through empty space to the side of the target, to be used as a reference for how the first has been distorted.

The first laser is moved around the object, hitting it from all angles, to build up a complete picture which is then rendered into a 3D model based on the data, using an algorithm developed by the authors.

A single Neuron, imaged in real-time

In addition, because neurons are semi-transparent, some information is obtained from the beam passing through them, and so their internal activity can also be monitored in real-time.

“Due to the technique’s precision, speed, and lack of invasiveness, it is possible to track minute changes in neuron properties in relation to an applied test drug and allow for a better understanding of what is happening,” Magistretti says. “What normally would take 12 hours in the lab can now be done in 15 to 30 minutes, greatly decreasing the time it takes for researchers to know if a drug is effective or not.”


Holograms reveal brain's inner workings

Determination of Transmembrane Water Fluxes in Neurons Elicited by Glutamate Ionotropic Receptors and by the Co-transporters KCC2 and NKCC1: A Digital Holographic Microscopy Study

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