Behold the entire nervous system of a mouse, revealed in unprecedented detail by turning the animal鈥檚 body completely transparent. This technique could help us better understand the workings of mammal brains and bodies.
Ali Ert眉rk of the Ludwig Maximilian University of Munich in Germany and his team have refined a technique called tissue clearing, so that the whole bodies of mice and rats can be studied in more detail than ever before. Other methods exist for making transparent rodents, but Ert眉rk鈥檚 technique also shrinks the body to around a third of its original size, making it possible to view the whole animal under a microscope, and subject it to detailed laser scanning for the first time.
This enabled the team to image all the nerve cell connections inside a mouse from head-to-toe, a feat never before accomplished, says Ert眉rk. 鈥淲e 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,鈥� he says.
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Travels in a mouse
The technique involves using a solvent to wash out all of a dead animal鈥檚 body water, and much of its fat too, over three or four days. This leaves the remaining tissue, including the bones, transparent, enabling much clearer, crisper microscope images.
By taking many laser scans and putting these images together, the team generated a 3D projection of a mouse, with its nervous system illuminated by a glowing green protein. The projection allows researchers to travel virtually through the mouse, examining all its neural connections.
The green colour in the above video comes from genetically engineering the mice to contain a green fluorescent protein. To visualise nerve cells or the brains of people after death, fluorescent antibodies that stick to cells and make them visible could be applied.
Transparent motivations
Ert眉rk鈥檚 team is using the technique to study how traumatic brain injuries in mice affect the central nervous system.
The team has already scaled the technique up for rats, which are 10 times the size of mice. 鈥淚t might be possible with larger animals, such as small monkeys, and possibly a whole human brain for the first time in the near future,鈥� says Ert眉rk.
Being able to examine deep inside human brains after death without cutting into them could be a crucial step in understanding the brain鈥檚 connectome 鈥� the entirety of its neural circuits. The hope is that comparing the connectome of a healthy person with those of people with disorders like Alzheimer鈥檚 disease, multiple sclerosis or schizophrenia, could help us understand exactly how these conditions affect the brain.
Journal reference: Nature Methods, DOI: 10.1038/nmeth.3964
