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A New Way to Read the Brain [in 3D!!]

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What if you were trying to learn language, but you could only see one letter at a time. Nothing before that letter, nothing after that letter, just a single letter. You can imagine how frustrating something like that might be, that is exactly what scientists have been dealing with when it comes to the brain. But a new innovation is changing that and with it, opening a whole new realm of possibilities.

Researchers from the labs at MIT and the University of Vienna have created an imaging system that shows neural activity throughout the brains of living animals. This technique, which is the first of its kind that can generate 3-D movies of entire brains at the millisecond timescale, could help scientists discover how neuronal networks process sensory information and generate behavior.

The team used the system to simultaneously image the activity of every neuron in a worm [Caenorhabditis elegans for those of you who are worm fanatics, and why not?]. They also imaged the entire brain of a zebrafish larva, offering a more complete picture of nervous system activity than has been previously possible.

“Looking at the activity of just one neuron in the brain doesn’t tell you how that information is being computed; for that, you need to know what upstream neurons are doing. And to understand what the activity of a given neuron means, you have to be able to see what downstream neurons are doing,” says Ed Boyden, an associate professor of biological engineering and brain and cognitive sciences at MIT. “In short, if you want to understand how information is being integrated from sensation all the way to action, you have to see the entire brain.”

The new approach could offer not just new insight on how the brain works, but help neuroscientists learn more about the biological basis of brain disorders. Boyden says, “The ability to survey activity throughout a nervous system may help pinpoint the cells or networks that are involved with a brain disorder, leading to new ideas for therapies.”

Neurons encode basically everything — sensory data, motor plans, emotional states, and thoughts — using electrical impulses called action potentials [which work by calcium ions which stream into each cell as it fires]. By engineering the fluorescent proteins to glow when they bind calcium, scientists can visualize this electrical firing of neurons. However, until now there has been no way to image this neural activity over a large volume of cells, in three dimensions, and at high speed.

To accomplish this feat the team used an idea based on a widely used technology called light-field imaging. The technique creates 3-D images by measuring the angles of incoming rays of light. Microscopes that perform light-field imaging have been developed previously by multiple groups, but in the study, the researchers optimized it, and applied it, for the first time, to imaging neural activity.

“If you have one light-emitting molecule in your sample, rather than just refocusing it into a single point on the camera the way regular microscopes do, these tiny lenses will project its light onto many points. From that, you can infer the three-dimensional position of where the molecule was,” says Boyden, a member of MIT’s Media Lab and McGovern Institute for Brain Research.

The researchers used this technique to image neural activity in the worm C. elegans, which happens to be the only organism for which the entire neural wiring diagram is known. This 1-millimeter worm has 302 neurons [just a few shy of the roughly 86 billion you and I have], each of which the researchers imaged as the worm performed natural behaviors, such as crawling. They also observed the neuronal response to sensory stimuli, such as smells.

The big downside to this technique is that the resolution is not as good as that of techniques that slowly scan a sample [which should be pretty obvious when you think about it]. With the current resolution you can see activity of individual neurons, but the researchers are now trying to improve it so the microscope could also be used to image parts of neurons, like the long dendrites that branch out from neurons’ main bodies. They also hope to speed up the computing process, which currently takes a few minutes to analyze one second of imaging data, which could provide useful when they try to step up the technique to larger brain sizes like ours.

The researchers also plan to combine this technique with optogenetics [ for those of you who didn’t click the link, it enables neuronal firing to be controlled by shining light on cells engineered to express light-sensitive proteins]. By stimulating a neuron with light and observing the results elsewhere in the brain, scientists could determine which neurons are participating in particular tasks.

This could help advance both the field of neurology and the field of optogenetics which is very exciting! Already know about optogenetics? You probably want the full study, which you can find —here!

Sources:
Prevedel R., Yoon Y.G., Hoffmann M., Pak N., Wetzstein G., Kato S., Schrödel T., Raskar R., Zimmer M. & Boyden E.S. & (2014). Simultaneous whole-animal 3D imaging of neuronal activity using light-field microscopy, Nature Methods, DOI:

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