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Nat Neurosci. 2019 Feb;22(2):317-327. doi: 10.1038/s41593-018-0301-3. Epub 2018 Dec 31.

Panoptic imaging of transparent mice reveals whole-body neuronal projections and skull-meninges connections.

Author information

1
Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians University Munich, Munich, Germany.
2
Graduate School of Systemic Neurosciences Munich, Munich, Germany.
3
Institute of Clinical Neuroimmunology, Klinikum der Universität München, Ludwig-Maximilians University Munich, Munich, Germany.
4
Biomedical Center, Ludwig-Maximilians University Munich, Munich, Germany.
5
Department of Computer Science and Institute for Advanced Study, Technical University of Munich, Munich, Germany.
6
Center for Translational Neuromedicine, Faculties of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
7
Center for Translational Neuromedicine, University of Rochester, New York, NY, USA.
8
Anatomy Institute, University of Leipzig, Leipzig, Germany.
9
Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.
10
Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians University Munich, Munich, Germany. ali.ertuerk@med.uni-muenchen.de.
11
Graduate School of Systemic Neurosciences Munich, Munich, Germany. ali.ertuerk@med.uni-muenchen.de.
12
Munich Cluster for Systems Neurology (SyNergy), Munich, Germany. ali.ertuerk@med.uni-muenchen.de.

Abstract

Analysis of entire transparent rodent bodies after clearing could provide holistic biological information in health and disease, but reliable imaging and quantification of fluorescent protein signals deep inside the tissues has remained a challenge. Here, we developed vDISCO, a pressure-driven, nanobody-based whole-body immunolabeling technology to enhance the signal of fluorescent proteins by up to two orders of magnitude. This allowed us to image and quantify subcellular details through bones, skin and highly autofluorescent tissues of intact transparent mice. For the first time, we visualized whole-body neuronal projections in adult mice. We assessed CNS trauma effects in the whole body and found degeneration of peripheral nerve terminals in the torso. Furthermore, vDISCO revealed short vascular connections between skull marrow and brain meninges, which were filled with immune cells upon stroke. Thus, our new approach enables unbiased comprehensive studies of the interactions between the nervous system and the rest of the body.

PMID:
30598527
PMCID:
PMC6494982
DOI:
10.1038/s41593-018-0301-3
[Indexed for MEDLINE]
Free PMC Article

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