한빛사 논문
Abstract
Kwanghun Chung1,2, JenelleWallace1, Sung-Yon Kim1, Sandhiya Kalyanasundaram2, Aaron S. Andalman1,2, Thomas J. Davidson1,2, Julie J. Mirzabekov1, Kelly A. Zalocusky1,2, Joanna Mattis1, Aleksandra K. Denisin1, Sally Pak1, Hannah Bernstein1, Charu Ramakrishnan1, Logan Grosenick1, Viviana Gradinaru2 & Karl Deisseroth1,2,3,4,*
1Department of Bioengineering, Stanford University, Stanford, California 94305, USA. 2CNC Program, Stanford University, Stanford, California 94305, USA. 3Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, California 94305, USA. 4Howard Hughes Medical Institute, Stanford University, Stanford, California 94305, USA.
*Correspondence to: Karl Deisseroth
Abstract
Obtaining high-resolution information from a complex system, while maintaining the global perspective needed to understand system function, represents a key challenge in biology. Here we address this challenge with a method (termed CLARITY) for the transformation of intact tissue into a nanoporous hydrogel-hybridized form (crosslinked to a three-dimensional network of hydrophilic polymers) that is fully assembled but optically transparent and macromolecule-permeable. Using mouse brains, we show intact-tissue imaging of long-range projections, local circuit wiring, cellular relationships, subcellular structures, protein complexes, nucleic acids and neurotransmitters. CLARITY also enables intact-tissue in situ hybridization, immunohistochemistry with multiple rounds of staining and de-staining in non-sectioned tissue, and antibody labelling throughout the intact adult mouse brain. Finally, we show that CLARITY enables fine structural analysis of clinical samples, including non-sectioned human tissue from a neuropsychiatric-disease setting, establishing a path for the transmutation of human tissue into a stable, intact and accessible form suitable for probing structural and molecular underpinnings of physiological function and disease.
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