Cortical Column and Whole Brain Imaging of Neural Circuits with Molecular Contrast and Nanoscale Resolution

Ruixuan Gao; Shoh M. Asano; Srigokul Upadhyayula; Pisarev Igor; Daniel E. Milkie; Tsung Li Liu; Singh Ved; Graves Austin; Grace H. Huynh; Yongxin Zhao; John Bogovic; Jennifer Colonell; Carolyn M. Ott; Christopher Zugates; Susan Tappan; Alfredo Rodriguez; Kishore R. Mosaliganti; Sean G. Megason; Jennifer Lippincott-Schwartz; Adam Hantman; Gerald M. Rubin; Tom Kirchhausen; Stephan Saalfeld; Yoshinori Aso; Edward S. Boyden; Eric Betzig

doi:10.1101/374140

Cortical Column and Whole Brain Imaging of Neural Circuits with Molecular Contrast and Nanoscale Resolution

Ruixuan Gao, Shoh M. Asano, Srigokul Upadhyayula, Pisarev Igor, Daniel E. Milkie, Tsung Li Liu, Singh Ved, Graves Austin, Grace H. Huynh, Yongxin Zhao, John Bogovic, Jennifer Colonell, Carolyn M. Ott, Christopher Zugates, Susan Tappan, Alfredo Rodriguez, Kishore R. Mosaliganti, Sean G. Megason, Jennifer Lippincott-Schwartz, Adam HantmanGerald M. Rubin, Tom Kirchhausen, Stephan Saalfeld, Yoshinori Aso, Edward S. Boyden, Eric Betzig

Research output: Contribution to journal › Article › peer-review

Abstract

Optical and electron microscopy have made tremendous inroads in understanding the complexity of the brain, but the former offers insufficient resolution to reveal subcellular details and the latter lacks the throughput and molecular contrast to visualize specific molecular constituents over mm-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, including synaptic proteins at dendritic spines, myelination along axons, and presynaptic densities at dopaminergic neurons in every fly neuropil domain. 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. One Sentence Summary Combined expansion and lattice light sheet microscopy enables high speed, nanoscale molecular imaging of neural circuits over large volumes.

Original language	English (US)
Journal	Unknown Journal
DOIs	https://doi.org/10.1101/374140
State	Published - Jul 23 2018
Externally published	Yes

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology(all)
Agricultural and Biological Sciences(all)
Immunology and Microbiology(all)
Neuroscience(all)
Pharmacology, Toxicology and Pharmaceutics(all)

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10.1101/374140

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Gao, R., Asano, S. M., Upadhyayula, S., Igor, P., Milkie, D. E., Liu, T. L., Ved, S., Austin, G., Huynh, G. H., Zhao, Y., Bogovic, J., Colonell, J., Ott, C. M., Zugates, C., Tappan, S., Rodriguez, A., Mosaliganti, K. R., Megason, S. G., Lippincott-Schwartz, J., ... Betzig, E. (2018). Cortical Column and Whole Brain Imaging of Neural Circuits with Molecular Contrast and Nanoscale Resolution. Unknown Journal. https://doi.org/10.1101/374140

Cortical Column and Whole Brain Imaging of Neural Circuits with Molecular Contrast and Nanoscale Resolution. / Gao, Ruixuan; Asano, Shoh M.; Upadhyayula, Srigokul; Igor, Pisarev; Milkie, Daniel E.; Liu, Tsung Li; Ved, Singh; Austin, Graves; Huynh, Grace H.; Zhao, Yongxin; Bogovic, John; Colonell, Jennifer; Ott, Carolyn M.; Zugates, Christopher; Tappan, Susan; Rodriguez, Alfredo; Mosaliganti, Kishore R.; Megason, Sean G.; Lippincott-Schwartz, Jennifer; Hantman, Adam; Rubin, Gerald M.; Kirchhausen, Tom; Saalfeld, Stephan; Aso, Yoshinori; Boyden, Edward S.; Betzig, Eric.

In: Unknown Journal, 23.07.2018.

Research output: Contribution to journal › Article › peer-review

Gao, R, Asano, SM, Upadhyayula, S, Igor, P, Milkie, DE, Liu, TL, Ved, S, Austin, G, Huynh, GH, Zhao, Y, Bogovic, J, Colonell, J, Ott, CM, Zugates, C, Tappan, S, Rodriguez, A, Mosaliganti, KR, Megason, SG, Lippincott-Schwartz, J, Hantman, A, Rubin, GM, Kirchhausen, T, Saalfeld, S, Aso, Y, Boyden, ES & Betzig, E 2018, 'Cortical Column and Whole Brain Imaging of Neural Circuits with Molecular Contrast and Nanoscale Resolution', Unknown Journal. https://doi.org/10.1101/374140

Gao, Ruixuan ; Asano, Shoh M. ; Upadhyayula, Srigokul ; Igor, Pisarev ; Milkie, Daniel E. ; Liu, Tsung Li ; Ved, Singh ; Austin, Graves ; Huynh, Grace H. ; Zhao, Yongxin ; Bogovic, John ; Colonell, Jennifer ; Ott, Carolyn M. ; Zugates, Christopher ; Tappan, Susan ; Rodriguez, Alfredo ; Mosaliganti, Kishore R. ; Megason, Sean G. ; Lippincott-Schwartz, Jennifer ; Hantman, Adam ; Rubin, Gerald M. ; Kirchhausen, Tom ; Saalfeld, Stephan ; Aso, Yoshinori ; Boyden, Edward S. ; Betzig, Eric. / Cortical Column and Whole Brain Imaging of Neural Circuits with Molecular Contrast and Nanoscale Resolution. In: Unknown Journal. 2018.

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abstract = "Optical and electron microscopy have made tremendous inroads in understanding the complexity of the brain, but the former offers insufficient resolution to reveal subcellular details and the latter lacks the throughput and molecular contrast to visualize specific molecular constituents over mm-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, including synaptic proteins at dendritic spines, myelination along axons, and presynaptic densities at dopaminergic neurons in every fly neuropil domain. 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. One Sentence Summary Combined expansion and lattice light sheet microscopy enables high speed, nanoscale molecular imaging of neural circuits over large volumes.",

author = "Ruixuan Gao and Asano, {Shoh M.} and Srigokul Upadhyayula and Pisarev Igor and Milkie, {Daniel E.} and Liu, {Tsung Li} and Singh Ved and Graves Austin and Huynh, {Grace H.} and Yongxin Zhao and John Bogovic and Jennifer Colonell and Ott, {Carolyn M.} and Christopher Zugates and Susan Tappan and Alfredo Rodriguez and Mosaliganti, {Kishore R.} and Megason, {Sean G.} and Jennifer Lippincott-Schwartz and Adam Hantman and Rubin, {Gerald M.} and Tom Kirchhausen and Stephan Saalfeld and Yoshinori Aso and Boyden, {Edward S.} and Eric Betzig",

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AU - Upadhyayula, Srigokul

AU - Igor, Pisarev

AU - Milkie, Daniel E.

AU - Liu, Tsung Li

AU - Ved, Singh

AU - Austin, Graves

AU - Huynh, Grace H.

AU - Zhao, Yongxin

AU - Bogovic, John

AU - Colonell, Jennifer

AU - Ott, Carolyn M.

AU - Zugates, Christopher

AU - Tappan, Susan

AU - Rodriguez, Alfredo

AU - Mosaliganti, Kishore R.

AU - Megason, Sean G.

AU - Lippincott-Schwartz, Jennifer

AU - Hantman, Adam

AU - Rubin, Gerald M.

AU - Kirchhausen, Tom

AU - Saalfeld, Stephan

AU - Aso, Yoshinori

AU - Boyden, Edward S.

AU - Betzig, Eric

N1 - Publisher Copyright: The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.

PY - 2018/7/23

Y1 - 2018/7/23

N2 - Optical and electron microscopy have made tremendous inroads in understanding the complexity of the brain, but the former offers insufficient resolution to reveal subcellular details and the latter lacks the throughput and molecular contrast to visualize specific molecular constituents over mm-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, including synaptic proteins at dendritic spines, myelination along axons, and presynaptic densities at dopaminergic neurons in every fly neuropil domain. 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. One Sentence Summary Combined expansion and lattice light sheet microscopy enables high speed, nanoscale molecular imaging of neural circuits over large volumes.

AB - Optical and electron microscopy have made tremendous inroads in understanding the complexity of the brain, but the former offers insufficient resolution to reveal subcellular details and the latter lacks the throughput and molecular contrast to visualize specific molecular constituents over mm-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, including synaptic proteins at dendritic spines, myelination along axons, and presynaptic densities at dopaminergic neurons in every fly neuropil domain. 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. One Sentence Summary Combined expansion and lattice light sheet microscopy enables high speed, nanoscale molecular imaging of neural circuits over large volumes.

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