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.

With some 70 billion neurons and hundreds of thousands of kilometres of circuits, the human brain is so complex that, for many years, it seemed impossible to reconstruct the network in detail. Each neuron is linked to about a thousand others by means of finely branched projections called dendrites and axons, and communicates with them using electrical signals. The connections between the cells are critical for brain function, so neuroscientists are keen to understand the structure of these circuits – the connectome – and to reconstruct it in a three-dimensional map. Since no computer is powerful enough yet for the task, researchers are dependent on the human eye. However, the sheer number of cellular connections contained in even the tiniest fragment of tissue makes the undertaking seem pointless – unless it is shared among a large number of people.

Moritz Helmstaedter, Kevin L. Briggman and Winfried Denk, scientists at the Max Planck Institute for Medical Research in Heidelberg, have now successfully tested this procedure. They developed a special software tool called RESCOP which summarises the results of several annotators to yield an overall picture. In this way, and with the support of over 70 students from Heidelberg University, they reconstructed a network of over 100 neurons from the retina in full detail.

The students used the KNOSSOS software developed by the team in Heidelberg to trace the connections between the neurons. It is no coincidence that the program is named after Crete’s legendary palace, renowned for its elaborate labyrinth: “Tracing the connections in the brain is at least as hard as finding your way out of a mythological labyrinth”, explains Moritz Helmstaedter.