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2 Publications

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    10/26/22 | Rapid reconstruction of neural circuits using tissue expansion and lattice light sheet microscopy
    Joshua L. Lillvis , Hideo Otsuna , Xiaoyu Ding , Igor Pisarev , Takashi Kawase , Jennifer Colonell , Konrad Rokicki , Cristian Goina , Ruixuan Gao , Amy Hu , Kaiyu Wang , John Bogovic , Daniel E. Milkie , Edward S. Boyden , Stephan Saalfeld , Paul W. Tillberg , Barry J. Dickson
    eLife. 2022 Oct 26:. doi: 10.7554/eLife.81248

    Electron microscopy (EM) allows for the reconstruction of dense neuronal connectomes but suffers from low throughput, limiting its application to small numbers of reference specimens. We developed a protocol and analysis pipeline using tissue expansion and lattice light-sheet microscopy (ExLLSM) to rapidly reconstruct selected circuits across many samples with single synapse resolution and molecular contrast. We validate this approach in Drosophila, demonstrating that it yields synaptic counts similar to those obtained by EM, can be used to compare counts across sex and experience, and to correlate structural connectivity with functional connectivity. This approach fills a critical methodological gap in studying variability in the structure and function of neural circuits across individuals within and between species.

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    07/25/18 | An unbiased template of the Drosophila brain and ventral nerve cord.
    Bogovic JA, Otsuna H, Heinrich L, Ito M, Jeter J, Meissner GW, Nern A, Colonell J, Malkesman O, Saalfeld S
    bioRxiv. 2018 Jul 25:. doi: 10.1101/376384

    The fruit fly Drosophila melanogaster is an important model organism for neuroscience with a wide array of genetic tools that enable the mapping of individuals neurons and neural subtypes. Brain templates are essential for comparative biological studies because they enable analyzing many individuals in a common reference space. Several central brain templates exist for Drosophila, but every one is either biased, uses sub-optimal tissue preparation, is imaged at low resolution, or does not account for artifacts. No publicly available Drosophila ventral nerve cord template currently exists. In this work, we created high-resolution templates of the Drosophila brain and ventral nerve cord using the best-available technologies for imaging, artifact correction, stitching, and template construction using groupwise registration. We evaluated our central brain template against the four most competitive, publicly available brain templates and demonstrate that ours enables more accurate registration with fewer local deformations in shorter time.

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