Brain cells shown live in vivid 3D
Researchers are working on an exciting new method to monitor the brain in real-time 3D.
An international team has created the new imaging system to reveal neural activity, helping to discover how neuron networks process sensory information and generate behaviour.
It is the first to generate 3D movies of an entire brain at the millisecond timescale.
The new technique employs the widely-used technology known as light-field imaging, which creates 3-D images by measuring the angles of incoming rays of light. In a new paper, researchers optimised the light-field microscope and applied it for the first time to imaging neural activity.
The team of researchers at MIT and the University of Vienna used the new system to simultaneously image the activity of every neuron in the worm Caenorhabditis elegans, as well as the entire brain of a zebrafish larva.
Their early work has already offered 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 and one of the leaders of the research team.
“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.”
“We don't really know, for any brain disorder, the exact set of cells involved,” 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 information — sensory data, motor plans, emotional states, and thoughts — using electrical impulses called action potentials, which provoke calcium ions to stream into each cell as it fires.
By engineering fluorescent proteins to glow when they bind calcium, scientists can visualize this electrical firing of neurons.
With a light-field imaging microscope, light emitted by the sample being imaged is sent through an array of lenses that refracts the light in different directions. Each point of the sample generates about 400 different points of light, which can then be recombined using a computer algorithm to recreate the 3-D structure.
“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.
The main downside of the technique so far has been its relatively low resolution compared to single-neuron scanning, but researchers say they are honing this side of the technology all the time.
The team also plans to combine this technique with optogenetics; which 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.
The project continues.