Whole-brain annotation and multi-connectome cell typing of Drosophila

Abstract The fruit fly Drosophila melanogaster has emerged as a key model organism in neuroscience, in large part due to the concentration of collaboratively generated molecular, genetic and digital resources available for it. Here we complement the approximately 140,000 neuron FlyWire whole-brain connectome 1 with a systematic and hierarchical annotation of neuronal classes, cell types and developmental units (hemilineages). Of 8,453 annotated cell types, 3,643 were previously proposed in the partial hemibrain connectome 2, and 4,581 are new types, mostly from brain regions outside the hemibrain subvolume. Although nearly all hemibrain neurons could be matched morphologically in FlyWire, about one-third of cell types proposed for the hemibrain could not be reliably reidentified. We therefore propose a new definition of cell type as groups of cells that are each quantitatively more similar to cells in a different brain than to any other cell in the same brain, and we validate this definition through joint analysis of FlyWire and hemibrain connectomes. Further analysis defined simple heuristics for the reliability of connections between brains, revealed broad stereotypy and occasional variability in neuron count and connectivity, and provided evidence for functional homeostasis in the mushroom body through adjustments of the absolute amount of excitatory input while maintaining the excitation/inhibition ratio. Our work defines a consensus cell type atlas for the fly brain and provides both an intellectual framework and open-source toolchain for brain-scale comparative connectomics.

Authors

Philipp Schlegel; Yijie Yin; Alexander Shakeel Bates; Sven Dorkenwald; Katharina Eichler; Paul Brooks; Daniel Han; Marina Gkantia; Marcia dos Santos; Eva J Munnelly; Griffin Badalamente; Laia Serratosa Capdevila; Varun Aniruddha Sane; Alexandra M. C. Fragniere; Ladann Kiassat; Markus William Pleijzier; Tomke Stürner; Imaan FM Tamimi; Christopher R Dunne; Irene Salgarella; Alexandre Javier; Siqi Fang; Eric Perlman; Tom Kazimiers; Sridhar R. Jagannathan; Arie Matsliah; Amy Sterling; Szi-chieh Yu; Claire McKellar; Krzysztof Kruk; Doug Bland; Zairene Lenizo; Austin T. Burke; Kyle Patrick Willie; Alexander S. Bates; Nikitas Serafetinidis; Nashra Hadjerol; Ryan Willie; Ben Silverman; John Anthony Ocho; Joshua Bañez; Rey Adrian Candilada; Jay Gager; Anne Kristiansen; Nelsie Panes; Arti Yadav; Remer Tancontian; Shirleyjoy Serona; Jet Ivan Dolorosa; Kendrick Joules Vinson; Dustin Garner; Regine Salem; Ariel Dagohoy; Jaime Skelton; Mendell Lopez; Thomas Stocks; Anjali Pandey; Darrel Jay Akiatan; James Hebditch; Celia David; Dharini Sapkal; Shaina Mae Monungolh; Varun Sane; Mark Lloyd Pielago; Miguel Albero; Jacquilyn Laude; Marcia dos Santos; David Deutsch; Zeba Vohra; Kaiyu Wang; Allien Mae Gogo; Emil Kind; Alvin Josh Mandahay; Chereb Martinez; John David Asis; Chitra Nair; Dhwani Patel; Marchan Manaytay; Clyde Angelo Lim; Philip Lenard Ampo; Michelle Darapan Pantujan; Daril Bautista; Rashmita Rana; Jansen Seguido; Bhargavi Parmar; John Clyde Saguimpa; Merlin Moore; Markus William Pleijzier; Mark Larson; Joseph Hsu; Itisha Joshi; Dhara Kakadiya; Amalia Braun; Cathy Pilapil; Kaushik Parmar; Quinn Vanderbeck; Christopher R Dunne; Eva J Munnelly; Chan Hyuk Kang; Lena Lörsch

Published

Oct 2, 2024

Journal or venue

Nature

DOI

10.1038/s41586-024-07686-5

Paper type

journal article

Source

Openalex