A 3D adult zebrafish brain atlas (AZBA) for the digital age.

Justin W Kenney,Olivia Young,Patrick E Steadman,Thomas Mueller,Maris Polanco,Meng Ting Shi,Paul W Frankland,Kristopher Covert,Saba Dubaishi

doi:10.7554/elife.69988

Abstract

Zebrafish have made significant contributions to our understanding of the vertebrate brain and the neural basis of behavior, earning a place as one of the most widely used model organisms in neuroscience. Their appeal arises from the marriage of low cost, early life transparency, and ease of genetic manipulation with a behavioral repertoire that becomes more sophisticated as animals transition from larvae to adults. To further enhance the use of adult zebrafish, we created the first fully segmented three-dimensional digital adult zebrafish brain atlas (AZBA). AZBA was built by combining tissue clearing, light-sheet fluorescence microscopy, and three-dimensional image registration of nuclear and antibody stains. These images were used to guide segmentation of the atlas into over 200 neuroanatomical regions comprising the entirety of the adult zebrafish brain. As an open source, online (azba.wayne.edu), updatable digital resource, AZBA will significantly enhance the use of adult zebrafish in furthering our understanding of vertebrate brain function in both health and disease.

Highlights

Uncovering general principles of neuroanatomical function and brain-behavior relationships requires the integration of findings across model organisms that range in complexity, organization, and accessibility (Brenowitz and Zakon, 2015; Marder, 2002; Yartsev, 2017)
Established as a model organism for developmental biology due to ease of domestication, high fecundity, and early life transparency (Parichy, 2015), the increased popularity of zebrafish is driven by recent advancements in brain imaging, molecular genetic manipulation, and behavior
We introduce a new resource for the zebrafish community: AZBA, a three-dimensional adult zebrafish brain atlas that can be downloaded or explored on the web. This resource will facilitate a wide variety of neurobiological studies using adult zebrafish aimed at dissecting neural circuits of behavior, understanding brain pathology, and discovering novel and conserved neuroanatomy

Summary

Introduction

Uncovering general principles of neuroanatomical function and brain-behavior relationships requires the integration of findings across model organisms that range in complexity, organization, and accessibility (Brenowitz and Zakon, 2015; Marder, 2002; Yartsev, 2017). Digital atlases enable exploration of brain structures in any arbitrary three-dimensional perspective and can be readily updated to incorporate new information such as patterns of gene expression and anatomical connectivity, as has been done for the mouse (Wang et al, 2020) Such features are important for fields like neurodevelopment and comparative neuroanatomy that rely on three-dimensional topologies to understand how specific brain regions develop and relate across species. By generating this resource using readily available techniques, AZBA can be continuously updated to reflect the latest findings in zebrafish neuroanatomy. We anticipate this becoming an indispensable resource as adult zebrafish continue to gain traction as a model organism in understanding the intricacies of the vertebrate brain

Results

Discussion

Background

Methods