Last year, Karl Deisseroth and his team at Stanford University announced the development of a technique to make whole issue samples transparent, while maintaining their cellular structure.

The technique, called CLARITY, turns whole, soft tissue samples – such as an entire brain – completely transparent while maintaining their cellular structure.

The technique’s real beauty and power is the retention of three-dimensional structures and the ease with which the entire course of a single or multiple neurons throughout the brain can be traced via molecular staining.

What usually prevents scientists from studying the brain’s wiring (the connectome) are lipids (fats) within the membranes of cells. This limits the size of samples which can be meaningfully analysed on a microscopic level.

With around 20 billion neurons in the brain and each brain being unique, deciphering the human connectome has, over recent years, been taken on as an international challenge. The difficulty of this task largely stemmed from physically small sample sizes, and in tracing neurons from one sample to the next.

Deisseroth, Professor of Bioengineering and of Psychiatry and Behavioural Sciences, and his team used a hydrogel (acrylamide) to suspend all of the cells of a mouse’s brain in a scaffold, keeping the cells internal machinery in the same place. Scientists are then able to remove the opaque fats from the system without altering the other parts of the cell.

This transparent brain and the hydrogel matrix within which it is encapsulated is permeable to light, and a large range of molecules. This allows for the use of molecular markers to elucidate specific chemicals and structures in particular neurons or neuronal groups, identifying their particular type and three-dimensional structure.

The use of this technique in the field of neuroscience and mental health will allow the study of how structural changes in disorders such as autism, schizophrenia or addiction relate to the altered function of the brain. Most encouragingly, the technique has been made freely available to the global scientific community, opening the flood gates for an explosion in neuroscience understanding with ramifications in many other areas.

 

Oli Purnell