The brain’s connectome – from branch to branch

Max Planck scientists develop new analytical tools for the fast and accurate reconstruction of neural networks

The human brain is the most complex of all organs, containing billions of neurons with their corresponding projections, all woven together in a highly complex, three-dimensional web. To date, mapping this vast network posed a practically insurmountable challenge to scientists. Now, however, a research team from the Heidelberg-based Max Planck Institute for Medical Research has developed a method for tackling the mammoth task. Using two new computer programs, KNOSSOS and RESCOP, a group of over 70 students mapped a network of more than 100 neurons – and they did so faster and more accurately than with previous methods.

 

In order to reconstruct a neural circuit, researchers start by staining the neurons of a section of tissue with heavy metals to make them visible. Using three-dimensional electron microscope images, they start at the cell body and follow the dendrites and axons, marking the branch point nodes on the screen. Then they use the computer to generate a three-dimensional image of the section. In this way, they work their way through the tangle of neurons bit by bit. It is a tedious undertaking: One person working alone with the currently available programs would take at least 30 years to reconstruct a path of 30 centimetres in length. Besides, these procedures are prone to error, since the branch points are not always easily recognised and the annotator’s attentiveness decreases with time.

The KNOSSOS software considerably reduces the time required: It is about 50 times faster than other programs used up to now. In addition, the RESCOP program now makes it possible for dozens of people to work on the reconstruction at the same time. Since the method is easily learned, even non-experts can use it. Most of the students worked from home and sent their results to the scientists via e-mail. The scientists were able to establish that the error rate of the best students was no higher than that of experienced neurobiologists. Moreover, its sophisticated algorithms enable RESCOP to detect and average out inaccuracies. This means that the reconstruction is not only faster, but also more reliable than before.

“For the first time ever, these new programs could make it possible for us to unravel the complicated neural network of the brain – a task far more complex than decoding the human genome”, says Winfried Denk. Next, the scientists plan to reconstruct a fragment of the mouse cerebral cortex, as this is where all the important mental processes occur.