Cellular-resolution atlas of the larval zebrafish brain

The larval zebrafish brain is small but displays the basic architecture that is conserved across vertebrates. Neuroanatomical studies have identified all the previously described nuclei and neuropil areas, which divide the larval brain into 128 mutually exclusive, collectively exhaustive (MECE) territories. We are using genetic tricks to stochastically label individual neurons with membrane-targeted fluorophores. Labeled neurons are then imaged by confocal microscopy at high resolution and reconstructed for quantitative morphological analysis. In order to compare neurons between individual fish, we have registered over 4,000 of them to a high-resolution, age-matched standard brain. We also continue to add gene expression and marker patterns to the standard brain. As of 2021, the set of markers includes hundreds of transgenic lines, HCR RNA in situ labels and antibody stainings. With support from a local supercomputing center, this atlas has become a web-accessible resource and visualization tool for the entire community.

Our group is advancing a holistic network model of the entire zebrafish brain. We are interested in the following questions:

• What is the wiring diagram of the brain and what general computational principles can we derive from it?
• What is the mesoscale (inter-areal) connectivity graph and how does it help us to understand brain function by separating processing streams into edges and nodes?
• How many discrete cell types exist in the vertebrate brain and how are they distinguishable on the genetic level?
• How do cells differentiate and assume their specific function in the context of neuronal circuits during development and growth?
• How does function (from brain-wide imaging) map onto structure (wiring patterns)?

Reference

A Cellular-Resolution Atlas of the Larval Zebrafish Brain
Michael Kunst, Eva Laurell, Nouwar Mokayes, Dominique Förster, Marco Dal Maschio, Herwig Baier
Neuron, May 2019