Whole-Brain Profiling of Cells and Circuits in Mammals by Tissue Clearing and Light-Sheet Microscopy.

Tissue clearing and light-sheet microscopy have a 100-year-plus history, yet these fields have been combined only recently to facilitate novel experiments and measurements in neuroscience. Since tissue-clearing methods were first combined with modernized light-sheet microscopy a decade ago, the performance of both technologies has rapidly improved, broadening their applications. Here, we review the state of the art of tissue-clearing methods and light-sheet microscopy and discuss applications of these techniques in profiling cells and circuits in mice. We examine outstanding challenges and future opportunities for expanding these techniques to achieve brain-wide profiling of cells and circuits in primates and humans. Such integration will help provide a systems-level understanding of the physiology and pathology of our central nervous system.
Competing Interests: Declaration of Interests H.R.U. is a co-inventor on patent applications covering the CUBIC reagents and a cofounder of CUBICStars Inc. P.J.K. is a co-inventor on patents and patent applications covering multi-view and adaptive light-sheet microscopy. P.O. is a cofounder of Certerra Inc. and Certego Therapeutics Inc.
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