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Science. 2019 Jan 18;363(6424). pii: eaau8302. doi: 10.1126/science.aau8302.

Cortical column and whole-brain imaging with molecular contrast and nanoscale resolution.

Author information

1
MIT Media Lab, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA.
2
McGovern Institute for Brain Research, MIT, Cambridge, MA 02139, USA.
3
Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147, USA.
4
Department of Cell Biology, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA.
5
Program in Cellular and Molecular Medicine, Boston Children's Hospital, 200 Longwood Avenue, Boston, MA 02115, USA.
6
Department of Pediatrics, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA.
7
arivis AG, 1875 Connecticut Avenue NW, 10th floor, Washington, DC 20009, USA.
8
MBF Bioscience, 185 Allen Brook Lane, Suite 101, Williston, VT 05495, USA.
9
Department of Systems Biology, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA.
10
MIT Media Lab, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA. esb@media.mit.edu betzige@janelia.hhmi.org.
11
Department of Biological Engineering, MIT, Cambridge, MA 02139, USA.
12
MIT Center for Neurobiological Engineering, MIT, Cambridge, MA 02139, USA.
13
Department of Brain and Cognitive Sciences, MIT, Cambridge, MA 02139, USA.
14
Koch Institute, MIT, Cambridge, MA 02139, USA.
15
Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147, USA. esb@media.mit.edu betzige@janelia.hhmi.org.
16
Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA.
17
Department of Physics, University of California, Berkeley, CA 94720, USA.
18
Howard Hughes Medical Institute, Berkeley, CA 94720, USA.
19
Helen Wills Neuroscience Institute, Berkeley, CA 94720, USA.
20
Molecular Biophysics and Integrated Bioimaging Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
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Contributed equally

Abstract

Optical and electron microscopy have made tremendous inroads toward understanding the complexity of the brain. However, optical microscopy offers insufficient resolution to reveal subcellular details, and electron microscopy lacks the throughput and molecular contrast to visualize specific molecular constituents over millimeter-scale or larger dimensions. We combined expansion microscopy and lattice light-sheet microscopy to image the nanoscale spatial relationships between proteins across the thickness of the mouse cortex or the entire Drosophila brain. These included synaptic proteins at dendritic spines, myelination along axons, and presynaptic densities at dopaminergic neurons in every fly brain region. The technology should enable statistically rich, large-scale studies of neural development, sexual dimorphism, degree of stereotypy, and structural correlations to behavior or neural activity, all with molecular contrast.

Comment in

PMID:
30655415
PMCID:
PMC6481610
[Available on 2019-07-18]
DOI:
10.1126/science.aau8302

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