Automated deep-phenotyping of the vertebrate brain

Allalou, Amin; Wu, Yuelong; Ghannad-Rezaie, Mostafa; Eimon, Peter M.; Yanik, Mehmet Fatih

doi:10.7554/elife.23379

Cited by 20 publications

(23 citation statements)

References 75 publications

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“…Observing neural activity across an entire brain at cellular resolution has long been a dream for neuroscientists. The small size and transparency of zebrafish larvae, along with genetically encoded activity sensors and new microscopy techniques, have made this fantasy a reality (Prevedel et al 2014;Tomer et al 2015;Allalou et al 2017). At the meeting, Karl Deisseroth, Ed Boyden, and Fatih Yanik presented distinct microscopy techniques to reveal the dynamics of entire zebrafish brains.…”

Section: Emerging Approaches: Dish Fish and Human Neurosciencementioning

confidence: 99%

Summary: Order and Disorder in Brains and Behavior

Kepecs

2018

Cold Spring Harb Symp Quant Biol

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System explored the tremendous recent progress in neuroscience and how these advances may be used to improve brain health and address psychiatric and neurological disorders. The Symposium explored a vast array of topics from cell types to cognition. My summary focuses on a few emerging themes. Innovative techniques were ever-present, opening up new experimental possibilities. The commoditization of many state-of-the-art technologies is pushing neuroscience beyond its artisanal ways. Another important theme was "circuits in the middle": Numerous presentations dissected cell type-specific circuits that connect different levels of analysis from molecules to behavior. These new technologies have enabled curiosity-driven investigations in animals to connect more directly with preclinical and clinical studies of human brain disorders. Numerous emerging approaches were presented in human neuroscience, bolstering the hope that circuit-specific manipulations will soon provide improved treatments for brain disorders.The seat of the soul and the control of voluntary movement-in fact, of nervous functions in general-are to be sought in the heart. The brain is an organ of minor importance… .-Aristotle, De motu animalium

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Section: Emerging Approaches: Dish Fish and Human Neurosciencementioning

confidence: 99%

Summary: Order and Disorder in Brains and Behavior

Kepecs

2018

Cold Spring Harb Symp Quant Biol

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“…Registration techniques have been recently used in zebrafish to map changes in whole-brain activity patterns to a reference atlas, thereby connecting activity with neuroanatomical information [8,59,60]. A similar approach has been applied to analyze brain-wide changes in gene expression in mutant embryos by using optical projection tomography to image chromogenic whole-mount in situ hybridization (WISH) stained samples for voxel-intensity analysis [7]. This method is excellent for analysis of WISH staining, as it utilizes a standard chromogenic staining protocol that produces sensitive and robust signals.…”

Section: Discussionmentioning

confidence: 99%

“…A major challenge now is to understand how these factors perturb neural development. The larval zebrafish is a model that enables a systematic search for subtle changes in brain architecture and function [7,8]. Live-imaging of the entire larval brain at single cell resolution allows visualization of whole brain microstructure and cell-type composition, and highly accurate registration of brains to a common reference facilitates comparisons between individuals.…”

Section: Introductionmentioning

confidence: 99%

Morphometric analysis and neuroanatomical mapping of the zebrafish brain

Gupta

Marquart

Horstick

et al. 2018

Methods

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Large-scale genomic studies have recently identified genetic variants causative for major neurodevelopmental disorders, such as intellectual disability and autism. However, determining how underlying developmental processes are affected by these mutations remains a significant challenge in the field. Zebrafish is an established model system in developmental neurogenetics that may be useful in uncovering the mechanisms of these mutations. Here we describe the use of voxel-intensity, deformation field, and volume-based morphometric techniques for the systematic and unbiased analysis of gene knock-down and environmental exposure-induced phenotypes in zebrafish. We first present a computational method for brain segmentation based on transgene expression patterns to create a comprehensive neuroanatomical map. This map allowed us to disclose statistically significant changes in brain microstructure and composition in neurodevelopmental models. We demonstrate the effectiveness of morphometric techniques in measuring changes in the relative size of neuroanatomical subdivisions in atoh7 morphant larvae and in identifying phenotypes in larvae treated with valproic acid, a chemical demonstrated to increase the risk of autism in humans. These tools enable rigorous evaluation of the effects of gene mutations and environmental exposures on neural development, providing an entry point for cellular and molecular analysis of basic developmental processes as well as neurodevelopmental and neurodegenerative disorders.

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“…(3)) as thresholding value. Then, a marker image is created by setting local maxima of I i inside A 2 (Eq. (4)) to 2, the frame of the image to 1 and every other voxels to 0 (Eq.…”

Section: Notationsmentioning

confidence: 99%

“…However, image-based screening approaches, which are using whole zebrafish embryos, are mainly performed on the basis of 2D images [17,19]. While 3D-based screening methods do exist, they are either using unconventional microscopy setups, or need multiple acquisitions of the same sample [2,8,14,15,21], which renders them unsuitable for large scale analysis.…”

Section: Introductionmentioning

confidence: 99%

Automated segmentation of thick confocal microscopy 3D images for the measurement of white matter volumes in zebrafish brains

Lempereur

Jenett

Machado

et al. 2020

Mathematical Morphology - Theory and Applications

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Tissue clearing methods have boosted the microscopic observations of thick samples such as whole-mount mouse or zebrafish. Even with the best tissue clearing methods, specimens are not completely transparent and light attenuation increases with depth, reducing signal output and signal-to-noise ratio. In addition, since tissue clearing and microscopic acquisition techniques have become faster, automated image analysis is now an issue. In this context, mounting specimens at large scale often leads to imperfectly aligned or oriented samples, which makes relying on predefined, sample-independent parameters to correct signal attenuation impossible.Here, we propose a sample-dependent method for contrast correction. It relies on segmenting the sample, and estimating sample depth isosurfaces that serve as reference for the correction. We segment the brain white matter of zebrafish larvae. We show that this correction allows a better stitching of opposite sides of each larva, in order to image the entire larva with a high signal-to-noise ratio throughout. We also show that our proposed contrast correction method makes it possible to better recognize the deep structures of the brain by comparing manual vs. automated segmentations. This is expected to improve image observations and analyses in high-content methods where signal loss in the samples is significant.

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Automated deep-phenotyping of the vertebrate brain

Cited by 20 publications

References 75 publications

Summary: Order and Disorder in Brains and Behavior

Summary: Order and Disorder in Brains and Behavior

Morphometric analysis and neuroanatomical mapping of the zebrafish brain

Automated segmentation of thick confocal microscopy 3D images for the measurement of white matter volumes in zebrafish brains

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