Light-sheet fluorescence expansion microscopy: fast mapping of neural circuits at super resolution

Neurophotonics
Jana BürgersMartin K Schwarz

Abstract

The goal of understanding the architecture of neural circuits at the synapse level with a brain-wide perspective has powered the interest in high-speed and large field-of-view volumetric imaging at subcellular resolution. Here, we developed a method combining tissue expansion and light-sheet fluorescence microscopy to allow extended volumetric super resolution high-speed imaging of large mouse brain samples. We demonstrate the capabilities of this method by performing two color fast volumetric super resolution imaging of mouse CA1 and dentate gyrus molecular-, granule cell-, and polymorphic layers. Our method enables an exact evaluation of granule cell and neurite morphology within the context of large cell ensembles spanning several orders of magnitude in resolution. We found that imaging a brain region of 1    mm 3 in super resolution using light-sheet fluorescence expansion microscopy is about 17-fold faster than imaging the same region by a current state-of-the-art high-resolution confocal laser scanning microscope.

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Citations

Nov 26, 2019·Advanced Science·Han-Eol ParkSung-Yon Kim
May 15, 2020·Optics Express·Anne StockhausenUlrich Kubitscheck
Dec 15, 2020·Molecular Autism·Arquimedes ChefferOliver Brüstle
Mar 11, 2021·Journal of the American Society of Nephrology : JASN·Annika Möller-KeruttThomas Weide
Feb 6, 2021·Journal of Neurochemistry·Callista B Harper, Karen J Smillie
Apr 5, 2021·Neurobiology of Disease·Brendan R Gallagher, Yongxin Zhao
Jun 22, 2021·Frontiers in Cellular Neuroscience·Daniel MingeChristian Henneberger

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Methods Mentioned

BETA
electron microscopy
light scattering
light microscopy
optical diffraction
fluorescence microscopy
fluorescence
confocal microscopy
Fluorescence Expansion
fluorescence imaging
chip

Software Mentioned

Windows
Airyscan
LabView
MATLAB
ZEN Black
Huygens
ZEN
LSFEM
Eclipse
Imaris

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