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Whole-brain annotation and multi-connectome cell typing of Drosophila
Nature ( IF 50.5 ) Pub Date : 2024-10-02 , DOI: 10.1038/s41586-024-07686-5
Philipp Schlegel, Yijie Yin, Alexander S. Bates, Sven Dorkenwald, Katharina Eichler, Paul Brooks, Daniel S. Han, Marina Gkantia, Marcia dos Santos, Eva J. Munnelly, Griffin Badalamente, Laia Serratosa Capdevila, Varun A. Sane, Alexandra M. C. Fragniere, Ladann Kiassat, Markus W. Pleijzier, Tomke Stürner, Imaan F. M. Tamimi, Christopher R. Dunne, Irene Salgarella, Alexandre Javier, Siqi Fang, Eric Perlman, Tom Kazimiers, Sridhar R. Jagannathan, Arie Matsliah, Amy R. Sterling, Szi-chieh Yu, Claire E. McKellar, Marta Costa, H. Sebastian Seung, Mala Murthy, Volker Hartenstein, Davi D. Bock, Gregory S. X. E. Jefferis

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 connectome1 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 connectome2, 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.



中文翻译:


果蝇的全脑注释和多连接组细胞分型



果蝇黑腹果蝇已成为神经科学中的关键模式生物,这在很大程度上是由于协作生成的分子、遗传和数字资源的集中。在这里,我们通过神经元类别、细胞类型和发育单位(半系)的系统和分层注释来补充大约 140,000 个神经元 FlyWire 全脑连接组1。在 8,453 种注释的细胞类型中,有 3,643 种先前在部分半脑连接组2 中提出,4,581 种是新类型,主要来自半脑子卷以外的大脑区域。尽管几乎所有的半脑神经元都可以在 FlyWire 中进行形态匹配,但为半脑提出的大约三分之一的细胞类型无法可靠地重新识别。因此,我们提出了细胞类型的新定义,即每个细胞组在数量上与不同大脑中的细胞比与同一大脑中的任何其他细胞更相似,我们通过对 FlyWire 和半脑连接组的联合分析来验证这一定义。进一步的分析定义了大脑之间连接可靠性的简单启发式方法,揭示了神经元数量和连接的广泛刻板印象和偶尔的变化,并通过调整兴奋性输入的绝对量为蘑菇体内的功能性稳态提供了证据,同时保持兴奋/抑制比。我们的工作为果蝇大脑定义了一个共有细胞类型图谱,并为大脑规模的比较连接组学提供了智能框架和开源工具链。

更新日期:2024-10-03
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