From The Quarterly, Summer 2013

Thanks to many years of work by a determined and talented team, researchers are able for the first time to image a whole, intact brain in three dimensions and obtain a virtually transparent view of its inner structure. The new technology, called CLARITY, involves an intricate process of replacing the brain’s fatty molecules, and their role of holding the brain together, with a clear transparent gel (called a hydrogel). Once complete, after about 9 days, researchers are then able to use 3-D imaging technology to see all the brain’s important structures from single neurons to populations of neurons and how they project, to axons, dendrites, synapses, etc.



This groundbreaking technique was developed by a multidisciplinary team led by Brain & Behavior Research Foundation Scientific Council Member and NARSAD Grantee Karl Deisseroth, M.D., Ph.D. (see Interview with a Researcher, p. 5). The research was reported online on April 10th in the journal Nature.



“Studying intact systems with this sort of molecular resolution and global scope to be able to see the fine detail and the big picture at the same time has been a major unmet goal in biology, and a goal that CLARITY begins to address,” said Dr. Deisseroth. “It enables researchers to study complex biological systems with high resolution without taking them apart.” The new imaging technology can be used to make any organ transparent, but it was the challenges of imaging the brain that motivated Dr. Deisseroth. He hopes the technology will lead to identification of brain malfunctions that lead to psychiatric disorders such as schizophrenia, depression and autism.



The research in this study was performed primarily on mouse brains, but the team also analyzed post-mortem brain tissue from a patient with autism spectrum disorder (ASD). They were able to see dendrites of neurons in the cortex joining together in ladder- like patterns in the ASD patient, a pattern not seen in typical brains.



Within a week of publication, the Deisseroth lab was abuzz with requests from dozens of labs wanting to learn about the new technology. And, as the lab did with their groundbreaking development of optogenetics technology, they intend to share it openly and widely. This kind of open sharing of breakthrough new approaches to understanding the brain and how it functions and can malfunction gives great reason for hope that improved treatments and even possibilities for prevention of mental illnesses are on our horizon.



The Takeaway

A technique named CLARITY that makes it possible for researchers to see through an intact, preserved brain and into its structures in exquisite detail is being openly shared with research labs around the world.



Karl Deisseroth, M.D., Ph.D.

Professor of Bioengineering and of Psychiatry and Behavioral Sciences

Stanford University

2005 NARSAD Young Investigator Grantee

Foundation Scientific Council Member