A large field-of-view, single-cell-resolution two- and three-photon microscope for deep and wide imaging

Abstract In vivo imaging of large-scale neuronal activity plays a pivotal role in unraveling the function of the brain's circuitry. Multiphoton microscopy, a powerful tool for deep-tissue imaging, has received sustained interest in advancing its speed, field of view and imaging depth. However,...

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Main Authors: Aaron T. Mok, Tianyu Wang, Shitong Zhao, Kristine E. Kolkman, Danni Wu, Dimitre G. Ouzounov, Changwoo Seo, Chunyan Wu, Joseph R. Fetcho, Chris Xu
Format: Article
Language:English
Published: SpringerOpen 2024-11-01
Series:eLight
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Online Access:https://doi.org/10.1186/s43593-024-00076-4
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author Aaron T. Mok
Tianyu Wang
Shitong Zhao
Kristine E. Kolkman
Danni Wu
Dimitre G. Ouzounov
Changwoo Seo
Chunyan Wu
Joseph R. Fetcho
Chris Xu
author_facet Aaron T. Mok
Tianyu Wang
Shitong Zhao
Kristine E. Kolkman
Danni Wu
Dimitre G. Ouzounov
Changwoo Seo
Chunyan Wu
Joseph R. Fetcho
Chris Xu
author_sort Aaron T. Mok
collection DOAJ
description Abstract In vivo imaging of large-scale neuronal activity plays a pivotal role in unraveling the function of the brain's circuitry. Multiphoton microscopy, a powerful tool for deep-tissue imaging, has received sustained interest in advancing its speed, field of view and imaging depth. However, to avoid thermal damage in scattering biological tissue, field of view decreases exponentially as imaging depth increases. We present a suite of innovations to optimize three-photon microscopy for large field-of-view imaging at depths unreachable by two-photon microscopy. These techniques enable us to image neuronal activities of transgenic animals expressing protein calcium sensors in a ~ 3.5-mm diameter field-of-view with single-cell resolution in the deepest cortical layer of mouse brains. We further demonstrate simultaneous large field-of-view two-photon and three-photon imaging, subcortical imaging in the mouse brain, and whole-brain imaging in adult zebrafish. The demonstrated techniques can be integrated into typical multiphoton microscopes to enlarge field of view for system-level neural circuit research.
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spelling doaj-art-d13c4a3b9eea4ebd9a9100ad8a630afd2024-12-15T12:07:08ZengSpringerOpeneLight2097-17102662-86432024-11-014111410.1186/s43593-024-00076-4A large field-of-view, single-cell-resolution two- and three-photon microscope for deep and wide imagingAaron T. Mok0Tianyu Wang1Shitong Zhao2Kristine E. Kolkman3Danni Wu4Dimitre G. Ouzounov5Changwoo Seo6Chunyan Wu7Joseph R. Fetcho8Chris Xu9School of Applied and Engineering Physics, Cornell UniversityDepartment of Electrical and Computer Engineering, Boston UniversitySchool of Applied and Engineering Physics, Cornell UniversityDepartment of Neurobiology and Behavior, Cornell UniversityHarvard T.H. Chan School of Public Health, Harvard UniversitySchool of Applied and Engineering Physics, Cornell UniversityDepartment of Molecular & Cellular Biology, Harvard UniversityMcGovern Institute for Brain Research at MITDepartment of Neurobiology and Behavior, Cornell UniversitySchool of Applied and Engineering Physics, Cornell UniversityAbstract In vivo imaging of large-scale neuronal activity plays a pivotal role in unraveling the function of the brain's circuitry. Multiphoton microscopy, a powerful tool for deep-tissue imaging, has received sustained interest in advancing its speed, field of view and imaging depth. However, to avoid thermal damage in scattering biological tissue, field of view decreases exponentially as imaging depth increases. We present a suite of innovations to optimize three-photon microscopy for large field-of-view imaging at depths unreachable by two-photon microscopy. These techniques enable us to image neuronal activities of transgenic animals expressing protein calcium sensors in a ~ 3.5-mm diameter field-of-view with single-cell resolution in the deepest cortical layer of mouse brains. We further demonstrate simultaneous large field-of-view two-photon and three-photon imaging, subcortical imaging in the mouse brain, and whole-brain imaging in adult zebrafish. The demonstrated techniques can be integrated into typical multiphoton microscopes to enlarge field of view for system-level neural circuit research.https://doi.org/10.1186/s43593-024-00076-4Three-photon microscopyTwo-photon microscopyLarge field of viewBrain imagingDEEPscope
spellingShingle Aaron T. Mok
Tianyu Wang
Shitong Zhao
Kristine E. Kolkman
Danni Wu
Dimitre G. Ouzounov
Changwoo Seo
Chunyan Wu
Joseph R. Fetcho
Chris Xu
A large field-of-view, single-cell-resolution two- and three-photon microscope for deep and wide imaging
eLight
Three-photon microscopy
Two-photon microscopy
Large field of view
Brain imaging
DEEPscope
title A large field-of-view, single-cell-resolution two- and three-photon microscope for deep and wide imaging
title_full A large field-of-view, single-cell-resolution two- and three-photon microscope for deep and wide imaging
title_fullStr A large field-of-view, single-cell-resolution two- and three-photon microscope for deep and wide imaging
title_full_unstemmed A large field-of-view, single-cell-resolution two- and three-photon microscope for deep and wide imaging
title_short A large field-of-view, single-cell-resolution two- and three-photon microscope for deep and wide imaging
title_sort large field of view single cell resolution two and three photon microscope for deep and wide imaging
topic Three-photon microscopy
Two-photon microscopy
Large field of view
Brain imaging
DEEPscope
url https://doi.org/10.1186/s43593-024-00076-4
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