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

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

doi:10.1126/science.aau8302

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

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

School of Medicine

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

106 Scopus citations

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.

Original language	English (US)
Article number	eaau8302
Journal	Science
Volume	363
Issue number	6424
DOIs	https://doi.org/10.1126/science.aau8302
State	Published - Jan 18 2019

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Gao, R., Asano, S. M., Upadhyayula, S., Pisarev, I., Milkie, D. E., Liu, T. L., Singh, V., Graves, A., Huynh, G. H., Zhao, Y., Bogovic, J., Colonell, J., Ott, C. M., Zugates, C., Tappan, S., Rodriguez, A., Mosaliganti, K. R., Sheu, S. H., Pasolli, H. A., ... Betzig, E. (2019). Cortical column and whole-brain imaging with molecular contrast and nanoscale resolution. Science, 363(6424), Article eaau8302. https://doi.org/10.1126/science.aau8302

Gao, R, Asano, SM, Upadhyayula, S, Pisarev, I, Milkie, DE, Liu, TL, Singh, V, Graves, A, Huynh, GH, Zhao, Y, Bogovic, J, Colonell, J, Ott, CM, Zugates, C, Tappan, S, Rodriguez, A, Mosaliganti, KR, Sheu, SH, Pasolli, HA, Pang, S, Xu, CS, Megason, SG, Hess, H, Lippincott-Schwartz, J, Hantman, A, Rubin, GM, Kirchhausen, T, Saalfeld, S, Aso, Y, Boyden, ES & Betzig, E 2019, 'Cortical column and whole-brain imaging with molecular contrast and nanoscale resolution', Science, vol. 363, no. 6424, eaau8302. https://doi.org/10.1126/science.aau8302

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title = "Cortical column and whole-brain imaging with molecular contrast and nanoscale resolution",

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.",

author = "Ruixuan Gao and Asano, {Shoh M.} and Srigokul Upadhyayula and Igor Pisarev and Milkie, {Daniel E.} and Liu, {Tsung Li} and Ved Singh and Austin Graves 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 Sheu, {Shu Hsien} and Pasolli, {H. Amalia} and Song Pang and Xu, {C. Shan} and Megason, {Sean G.} and Harald Hess 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 - Pisarev, Igor

AU - Milkie, Daniel E.

AU - Liu, Tsung Li

AU - Singh, Ved

AU - Graves, Austin

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 - Sheu, Shu Hsien

AU - Pasolli, H. Amalia

AU - Pang, Song

AU - Xu, C. Shan

AU - Megason, Sean G.

AU - Hess, Harald

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

PY - 2019/1/18

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AB - 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.

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

Abstract

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