Zebrafish brain atlases: a collective effort for a tiny vertebrate brain

Abstract

In the past two decades, digital brain atlases have emerged as essential tools for sharing and integrating complex neuroscience datasets. Concurrently, the larval zebrafish has become a prominent vertebrate model offering a strategic compromise for brain size, complexity, transparency, optogenetic access, and behavior. We provide a brief overview of digital atlases recently developed for the larval zebrafish brain, intersecting neuroanatomical information, gene expression patterns, and connectivity. These atlases are becoming pivotal by centralizing large datasets while supporting the generation of circuit hypotheses as functional measurements can be registered into an atlas' standard coordinate system to interrogate its structural database. As challenges persist in mapping neural circuits and incorporating functional measurements into zebrafish atlases, we emphasize the importance of collaborative efforts and standardized protocols to expand these resources to crack the complex codes of neuronal activity guiding behavior in this tiny vertebrate brain.

Keywords: brain atlas; calcium imaging; circuit reconstruction; open-access datasets; whole-brain imaging; zebrafish.

Fig. 1

Workflow of brain mapping in the larval zebrafish. (a) Serial dual-color imaging of multiple fluorescently labeled larvae (channel 1, Tg (elavl3: H2b-GCaMP6s) and channel 2, anti-tyrosine hydroxylase immunolabeling). (b) Registration of multiple structural labels to generate a template brain (nuclear GCaMP channel). (c) Alignment of multiple structural labels onto a template brain to generate an atlas; background images and markers taken from Z-Brain Atlas. (d) Simultaneous visual stimulation, behavior, and whole-brain calcium imaging; neuronal response profiles are identified from the data. (e) Neuron centroids are mapped into distinct anatomical regions of the atlas; background image and regions taken from mapZebrain atlas. (f) Following functional measurements across fish, functional maps are compared with structural data to identify putative circuit models that can then be validated experimentally; neurons and markers taken from mapZebrain atlas. Panels (d)–(f) reflect purely hypothetical experiments and circuits. Orientations: A, anterior; P, posterior; L, left; and R, right.