Scientists Succeed in Mapping a "Labyrinth" of Neurons

Researchers from Johns Hopkins University have successfully mapped out the immensely convoluted pathways of cholinergic neurons - the largest nerve cells in the brain and the first cells to break down during Alzheimer's disease.

"For us, this was like scaling Mount Everest," neuroscientist Jeremy Nathans said in a statement.

According to Nathans, the immense size and labyrinthine quality of cholinergic neurons made mapping them extremely difficult. However, the effort was worth it, he says, because understanding the path of these nerve cells helps experts understand how Alzheimer's disease progresses.

"This work reveals the amazing challenges that cholinergic neurons face every day. Each of these cells is like a city connected to its suburbs by a single, one-lane road, with all of the emergency services located only in the city," Nathans explained. "You can imagine how hard it would be in a crisis if all of the emergency vehicles had to get to the suburbs along that one road. We think something like this might be happening when cholinergic neurons [are] trying to repair the damage done by Alzheimer's disease."

According to a study, authored by Nathans and published in the journal eLife, until now, the actual size, shape and territory covered by cholinergic neurons has been unknown.

To finally achieve this mapping, Nathans and his colleagues programmed several cholinergic neurons in lab mice to make a protein that could be seen via a colored chemical reaction called a marker. The key to this, Nathans explained, was to mark only a few branches of neurons at a time, because if all the neurons - with their thousands of branch points - were to be highlighted, all the team would see is a blob of color.

The researchers also used the same mapping technique in mice with Alzheimer's disease, which made them realize that their branches were fragmented and disintegrating.

Nathans hopes these results will allow for future researchers to "form and test better hypotheses about what goes wrong with [neurons] during disease."

The study was initially published in eLife on May 7.