New view of the nervous system


Rebecca Pool

Tuesday, March 12, 2019 - 14:15
Image: Neurons inside a freely-moving fruit fly larvae [Hillman and Grueber labs/Columbia's Zuckerman Institute]
US-based researchers have used high-speed volumetric microscopy to create 3D live-action videos of individual nerve cells moving, stretching and switching on, inside crawling fruit fly larvae.
Data gleaned from 'SCAPE' - a cutting-edge microscope developed at Columbia University to image neurons - reveals how proprioceptive neuron cells work together to provide feedback about body position, essential for coordinated movement.
"We know that the brain receives sensory signals though electrical pulses passed along neurons, but we didn't understand why some kinds of neurons are located in specific positions, or how particular signalling patterns represented different movements," says Dr Wesley Grueber, from Columbia's Mortimer B. Zuckerman Mind Brain Behavior Institute.
"To understand this process, we needed to know what signals the neurons are sending while the larva crawled around unconstrained," he adds.
As Rebecca Vaadia from the Grueber lab points out: "Although we could make larvae whose neurons were labelled with fluorescence flash as they fired, we had great difficulty imaging them."
"Even our fastest microscopes required the specimen to be constrained to move unnaturally slowly, so we could never truly capture neural activity that reflected the animal's natural, unencumbered movements until we began using SCAPE," she says.
First described by Professor Elizabeth Hillman from Biomedical Engineering at Columbia Engineering, and colleagues in 2015, SCAPE (swept confocally aligned planar excitation) microscopy forms 3D images of living organisms by scanning them with a laser light sheet.
This light sheet can be both projected and detected through a single, stationary objective lens, with SCAPE delivering 3D imaging speeds that are up to 500 times faster than conventional microscopes that scan objects point by point.
To analyse the massive amounts of imaging data gathered by SCAPE during larvae analysis, the researchers developed algorithms that tracked each proprioceptive cell, and determined exactly when it was active as the body compressed and extended during crawling.
High-speed, 3D SCAPE microscope captures live videos of fruit fly nerve cells in action. [Wenze Li and Rebecca Vaadia/Hillman and Grueber Labs/Columbia's Zuckerman Institute]
"We saw that the position of each cell made it sensitive to specific changes to the body's overall shape, and when we lined up all of the neurons' signals, we saw that these generated a detailed sequence of signals that reflected each body part's movement," highlights Dr Wenze Li from the Hillman lab. "It was like a beautiful machine."
"Our experiments consistently showed that each of the proprioceptor neurons reacted differently as the larvae crawled along, an observation that could not have been made if the larvae had been constrained," adds Grueber. "We saw, in real time, how some neurons fired when the animal's body stretched, while others fired when it compressed."
Researchers had long hypothesized that proprioception came with redundancy because switching off neurons made the larva crawl more slowly.
However, the latest results indicate that each neuron has its own slightly different role to play, and is positioned precisely to sense specific aspects of the animals' movement.
The researchers have also demonstrated that this rule did not just hold for crawling, but was important for encoding more complicated movements.
"We've demonstrated that SCAPE can track and map the proprioceptive neurons in a crawling fruit fly larva, and it is just the first of many studies that can now explore the fly and nervous systems of other animals," says Li. "We can now literally label any type of cell and find out what it is doing when the animal is moving, eating or even forming a memory; the possibilities are endless."
Learn more at bioRxiv.
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