In the Jan. 7 issue of Cell, Scientists in Columbia have created a coloring method, known as NeuroPAL (a Neuronal Polychromatic Atlas of Landmarks), which allows it possible to classify any single neuron in the mind of a worm—at least in experiments with Caenorhabditis elegans (C. elegans), a worm species widely used in biological science.

"Being able to identify neurons, or other types of cells, using color can help scientists visually understand the role of each part of a biological system," Coauthor Yemini said according to a press release. "That means when something goes wrong with the system, it may help pinpoint where the breakdown occurred."

There are some 86 billion neurons, or nerve cells, in the human brain, woven together through an approximate 100 trillion links, or synapses. Each cell has a purpose that enables us to transfer muscles, control our environment, make memories, and much more.

A NeuroPAL worm coiled into an O-shape with the head and tail touching each other at the top of the ring. Every neuron (the colored dots) can be identified by its color. The colors are added with fluorescent proteins using a newly developed genetic engineering technique. Credit: Eviatar Yemini

Despite the large amount of neurons and interactions, there is quite a lot we don't know regarding how neurons function together to give rise to thinking or action.

NeuroPAL, a procedure that utilizes genetic approaches to "paint" neurons with a fluorescent marker, enables, for the first time ever, scientists to be able to recognize each neuron during an entire animal's nervous system, when it is in operation.

The scientists established two software programs to perform their research: one that recognizes all the neurons in colorful photographs of NeuroPAL worms and a second that brings the NeuroPAL approach beyond the worm by creating ideal coloring for possible methods of identifying every form of cell or tissue in any organism that requires genetic manipulation.

"We used NeuroPAL to record brainwide activity patterns in the worm and decode the nervous system at work," said Eviatar Yemini, a postdoctoral researcher in the Department of Biological Sciences at Columbia and lead author of the study.

As the colors are painted onto the DNA of the neuron and related to particular genes, it is therefore possible to use the colors to show whether certain particular genes are present or missing from a cell.

The researchers said that the technique's innovation could quickly be overwhelmed by the findings it makes possible. Hobert and Yemini released NeuroPAL to the research community in anticipation of their Cell publishing, and many experiments have already been reported demonstrating the tool's usefulness.

"It's amazing to 'watch' a nervous system in its entirety and see what it does," said Oliver Hobert, professor in the Department of Biological Sciences at Columbia and a principal investigator with the Howard Hughes Medical Institute. "The images created are stunning-- brilliant spots of color appear in the worm's body like Christmas lights on a dark night."