© 2013 Nature America, Inc. All rights reserved. University, Stanford, California, USA. Correspondence should be addressed to K.C. ( 3 1 tissue intact of layers cellular few first the than deeper phenotyping of molecular forms for diffusion macromolecule to barriers creating space, extracellular little leave processes neural intertwined seamlessly system, In nervous central the mammalian say nothing of subsequent data curation and analysis). (to challenge formidable a is tissue neural from tion system. complex this contribute to the study in of and dysfunction function nation with other methods tion at the resolution of single cells. Alone or in informa combi molecular-phenotype with along collected research neuroscience of fields many for important information projection the anatomical- of has extraction rapid facilitate to potential CLARITY functionality. and accessibility increased for elements exogenous with replaced and a into are components removed tissue form in hybrid which tissue biological intact transform to used be patterns. projection CLARITY distinct many by cell represented of type each with types, cell distinct genetically of hundreds least at likely them among present, are neurons of billions many diversity; and scale both of in terms complex are brains staggeringly Mammalian mapping with approach, relevant exogenous permeable structure, hybrid of removal within hydrogel-based With Kwanghun Chung C 508 Received 18 Ma Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, California,Department USA. of Bioengineering, Stanford University, Stanford, California, USA. perspective

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an anatomical foundation that could help researchers decipher decipher researchers help could that foundation anatomical an w example, (for maps macroscale functional or structural animal- of activity an imaging (via in example, For subject brain in which a set opportunity. particular of neurons becomes known an and ­challenge method. registration Nissl-like a as useful ticularly CLARITY with compatible is staining DAPI to brain navigate regions of and identify interest markers (which are dense yet can distinct) be as useful landmarks staining broadly histology, conventional in As important. ularly partic becomes CLARITY of capability phenotyping ­molecular R o The authors declare competing financial interests: details are available in the COMPETING FINANCIA Fund Career Award at the Scientific Interface. Reeves, Gatsby, and Yu Foundations. K.C. is supported by the Burroughs Wellcome and Plasticity to Accelerate Injury Recovery program, and the Wiegers, Snyder, Abuse and the Defense Advanced Research Projects Agency Reorganization Hughes Medical Institute. K.D. is also funded by the National Institute on Drug Foundation, the President and Provost of Stanford University, and the Howard of Mental Health, as well as by the National Science Foundation, the Simons Transformative Research Award (TR01) to K.D. from the National Institute support. This work was funded by a US National Institutes of Health Director’s We acknowledge all members of the Deisseroth laboratory for discussions and A ( online able avail are methodology the establish to user general the help enable may that Resources tissues. and development cells of including relationships and function, organism and organ tissue, normal of study the for as well as conditions clinical other and disease autoimmune infection, cancer, including states logical patho of prognosis and diagnosis evaluation, the for and explored health to linked patterns disease brain-activity of meaning the to conceptually link future high-resolution activity maps activity help high-resolution future link also may conceptually to CLARITY data. experimental of the of types the different registration the require for will workflows but efficient of neuroscience development preclinical or clinical basic both and in questions fundamental address to used be could approach This value. substantial of be would partners) nection con their (and cells same those on information molecular and wiring brain-wide obtain and preparation same the clarify then to dysfunction, or function behavioral specific a in involved be 7. 6. 5. 4. 3. 2. 1. c o n eprints ckno

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