A circuit diagram of the mouse brain: scientists aim to analyse mouse brain under electron microscope

What happens in the brain when we see, hear, think and remember? To be able to answer questions like this, neuroscientists need information about how the millions of neurons in the brain are connected to each other.

Scientists at the Max Planck Institute for Medical Research in Heidelberg have taken a crucial step towards obtaining a complete circuit diagram of the brain of the mouse, a key model organism for the neurosciences.

The research group working with Prof Dr Winfried Denk has developed a method for preparing the whole mouse brain for a special microscopy process. With this, the resolution at which the brain tissue can be examined is so high that the fine extensions of almost every single neuron are visible.

Neurons transmit information through their extensions – the axons – and form a complex network of connections, which provides the basis for all information processing in the brain. Analysing this network under the microscope is one of the biggest challenges facing the neurosciences. Most axons are less than one micrometre thick, some even smaller than 100 nanometres.

''The electron microscope is the only microscope with a high enough resolution to enable individual axons lying next to each other to be distinguished from each other,'' says Dr Denk. Despite their minute diametre, axons can become very long and extend from one end of the brain to the other. To obtain an overall picture of a brain, the researchers have to analyse large pieces of tissue.

In 2004, scientists working with Denk developed a new method that enabled them to do just this - ''serial block-face'' scanning electron microscopy. To examine tissue using this method, it must be fixed, stained and embedded in synthetic material.