Scientists have published the most detailed pictures ever of nerve endings in mice, applying a decade-old technique known as SNAP-tagging to living neurons for the first time. The resulting images show individual nerves, touch receptors, and hair follicles stained in brilliant fluorescent colors that look more like abstract art than cutting-edge microscopy.
"It's seeing things we've never seen before," Paul Heppenstall, whose lab at the European Molecular Biology Laboratory (EMBL) in Italy developed the new technique, tells The Verge. "Things we've imagined were there but that we've not been able to see. Its high definition: making these elements stand out clear against the background."
"It's shocking the first time you see it."
Heppenstall says his favourite image shows hundreds of nerve endings just below the surface of the skin (top image, below). "It's shocking the first time you see it," he says. "Normally you'd just see the big fat one without any idea that all these other fibres are there. That was a stunning example."
The images produced by the team at EMBL are notable because although skin samples are easy to collect and maintain in a lab environment, they're notoriously resistant to analysis by microscopy. "The problem is that it's a very impermeable tissue," says Heppenstall. "It's very difficult to get things like antibodies and conventional labels in. It also has a background fluorescence. So if you shine a blue light on it [used in conventional imaging methods] it fluoresces green, which means you can’t see anything."
SNAP-tagging overcomes this issue by using a special protein that can bind itself to artificial dies and is produced in the skin of genetically-engineered mice. These dies are not only small enough to cross through the skin’s barriers (remember, this is the substance that does such a good job of keeping germs and microbes out of your body) but are also the right color to stand out against their fluorescent background. It’s this combination of chemical and biological expertise that produces such startling images.
The next step is to image whole circuits in action in the brain or spinal cord
And it’s not the end of the work either. Heppenstall says his ultimate aim is to not only identify individual neurons, but record them in action. "Eventually I'd like to be able to do this in brains or in spinal cords," he says. "Make this tissue transparent and then look at whole circuits." For example, research could change the temperature of a skin sample and watching this signal move through the nervous system. "At the moment we're just looking at where they go and what they look like," says Heppenstall, "but we want to see them actually transmitting information next."
- The red lines show free nerve endings split into "an incredible number of branches." Image: EMBL/L.Castaldi
- The nerve endings in red are formed into 'baskets' around the base of each hair follicle (in blue). Image: EMBL/L.Castaldi
- Previous methods attempted to use antibodies to stain nerves, but they couldn't make their way through the skin. Image: EMBL/L.Castaldi
- Dyeing the nerves in red - or near-infrared - allows researchers to see in far greater detail than ever before. Image: EMBL/L.Castaldi
- This image shows a bundle of nerves that relays information from touch receptors on the skin to the spinal cord and brain. Image: EMBL/L.Castaldi