CLARITY Makes Brains “See-Through”
The science community received big news out of California last week as Karl Deisseroth and his team of researchers from the Department of Bioengineering at Stanford University had their paper concerning their newly developed CLARITY brain imaging technique published in Nature. The most astounding aspect of the newly released technique is that is creates a “see-through” brain that can be anatomically analyzed in a number of ways. This method truly is a game-changer as it revolutionizes how neuroscientists are able to view brain tissue and allows for a clearer view of the big picture. In this case the big picture is an intact, whole brain.
The technique operates on the idea lipids in the bilayer of a cell’s plasma membrane block visible light. This is why the brain is normally not transparent. Removing these lipids but still keeping the other parts of the cell and its environment intact would render the brain “see-through” and allow for much easier imaging of large pieces of brain tissue, if not the whole brain at once. This idea is carried out by taking the brain and infusing it with acrylamide, which binds proteins, nucleic acids and other molecules, then heating the tissue to form a mesh that holds the tissue together. The brain is then treated with SDS detergent to remove the light-blocking lipids resulting in a stable brain-hydrogel hybrid. From here the transparent tissue can be fluorescently labeled for certain cells and analyzed. Through the whole process there is less than 10% protein loss in the brain tissue compared to around 41% for other current methods. This is an amazing improvement!
Example of brain image produced by CLARITY from neurons in an intact mouse hippocampus. (http://med.stanford.edu/ism/2013/downloads/CLARITY/CLARITY_stained.jpg)
Until now it has been common practice to use histology to analyze brain tissue in a study. This method involves slicing a section of brain up into extremely small pieces and dying certain slices for various cells and molecules of interest. If a researcher wants any idea of the bigger picture he/she must reconstruct the brain from these small slices. With the CLARITY technique slicing the brain up is no longer necessary. Never before has it been so easy to view full brains, or sections of brain, down to the cellular and molecular level. It is now easy to follow the trajectory of a single neuron through the whole brain.
The development of this brain imaging method comes at a time when much money is being put into uncovering the complete biological workings of the human brain. President Obama has announced his BRAIN initiative and the US National Institute of Health is working on its Human Connectome Project. CLARITY has big potential use for these initiatives and as the technique is refined it seems that it will have a large role in uncovering more about the elusive question of how our brains really work.
For more information on CLARITY view this video on Nature’s website:
http://www.nature.com/news/see-through-brains-clarify-connections-1.12768
– J. Daniel Bireley
Sources:
Structural and molecular interrogation of intact biological systems – Nature
See Through Brains Clarify Connections – Nature
