Research enhances CLARITY of the brain in neurological disease
A major challenge to researchers studying the brain has been the inability to study a fully intact brain, from both the global and microscopic perspectives. For example, researchers might want to examine the way a chemical interacts with brain cells, or neurons, both in the context individual neurons and of long neural circuits across the entire brain. Previously, researchers had to choose either to study a fully intact brain, which involves a lengthy sample preparation process and potential structural dissimilarities compared to the original organ, or to study small sections of the brain where one can examine fine molecular and cellular interactions without knowledge of the original complex structure of the neural circuit and structure of the intact brain. Dr. Karl Deisseroth, a 2012 Transformative Research Awardee from Stanford University and his colleagues, have combined tools from the fields of chemical engineering, computational optics, and molecular genetics to develop a new technology to solve this problem by transforming a fully intact mouse brain into a completely clear gel-based brain with all structural and molecular integrity intact. This new technology, named Clear Lipid-exchanged Anatomically Rigid Imaging/immunostaining-compatible Tissue hYdrogel (CLARITY) replaces lipids, or fats, which make the brain appear white outside of the body, and help form the structural basis for the brain, with a clear gel-like material that binds to cells, proteins, DNA, RNA, and other small molecules in the brain. The result is a completely clear brain with a gel-like consistency that maintains the same molecular and cellular relationships and structure as the original brain.
The new process, allows researchers to fluorescently tag small molecules and specific cell types to visualize individual molecular interactions as well as entire cellular networks in 3-D providing insight at both the molecular and whole system level which previously was not possible. CLARITY can be used by researchers to observe fine details of brains from animals and human patients with symptomatic neurological diseases without losing the larger-scale whole system perspective, potentially leading to new insights into diseases that affect the brain.
- Read more about this exciting new technology and watch videos of mouse brains transformed using CLARITY in the NIH Press Release here
- Read about this exciting new technology in the NIH Director’s Blog here
- Read the New York Times Article here
Chung K, Wallace J, Kim S-Y, Kalyanasundaram S, Andalman AS, Davidson TJ, Mirzabekov JJ, Zalocusky KA, Mattis J, Denisin AK, Pak S, Bernstein H, Ramakrishnan C, Grosenick L, Gradinaru V, Deisseroth K. Structural and molecular interrogation of intact biological systems. Nature, April 10, 2012. DOI: 10.1038/Nature12107.