A research team at the Ludwig Maximilians University of Munich in Germany have achieved an unprecedented feat - they have captured a visual representation for all nerve cell connections inside a mouse.
“We imaged the complete central nervous system of mice, and you can track individual cells several centimetres long that reach from the brain right through to the tip of the spinal cord,” lead author Ali Ertürk tells New Scientist.
To do this, they immersed a dead mouse’s body in a special solvent, washing out water and fat over several days, and eventually reducing the body size of the animal up to 65 per cent. The leftover tissue, including things like skin, bones and genetically modified fluorescent protein, was rendered translucent and the whole animal had shrunk so much, it could fit into a standard microscope.
Thus the researchers were able to study the nervous system in fine detail, including a close-up look at optic nerve protrusion and even the tiny nerves that let a mouse move its whiskers. The results were published yesterday in Nature Methods.
It’s not the first time scientists have managed to create a somewhat disturbing translucent mouse model, although arguably this one is the most workable yet - pliable, yet sturdy.
In 2014, researchers at Caltech employed a different method, which required removing the animal’s skin, and then pumping the mouse’s circulatory system full of ‘tissue-clearing reagents’ (a substance much like detergent).
Within two weeks, they had a perfectly translucent mouse-blob they could use to visualise specific cells under a microscope with the help of fluorescent highlighters.
These methods aren’t developed to simply put you off your lunch, however. Researchers are experimenting with tissue clearing because certain structures - and nerve cells in particular - are basically impossible to study in their connected, complicated state if you have to dissect the sample and look at it piece by piece.
For example, by looking at the nervous system of a whole animal at once, it’s possible to map it, and use that knowledge to determine how a certain treatment, such as electrical stimulation, is going to travel through the individual nerve cells, and what effects that might have on connected areas.
The “detergent method” can also be used for finding specific cells in a human cancer biopsy sample, for example - something that is much trickier when you have to slice a sample really finely, losing the 3-dimensional whole.
Ertürk team’s method could also mean good news for lab mice. “By generating whole mouse atlases and databases it can reduce the resources and number of animals needed in experimental research,” the authors write in this week’s paper.
Ultimately, a successful and scalable method for rendering tissue transparent is a step towards unlocking the mind-boggling complexity of the human brain - if we can apply a tissue clearing method on a whole, intact brain, then all those myriad nerve cell connections will become clear as day.