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High-throughput mapping of mesoscale connectomes in individual mice

Longwen Huang, View ORCID ProfileJustus M Kebschull, Daniel Furth, View ORCID ProfileSimon Musall, View ORCID ProfileMatthew T Kaufman, View ORCID ProfileAnne K Churchland, Anthony M Zador
doi: https://doi.org/10.1101/422477
Longwen Huang
Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA
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Justus M Kebschull
Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USAWatson School of Biological Sciences, Cold Spring Harbor, NY 11724, USA
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Daniel Furth
Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA
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Simon Musall
Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA
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Matthew T Kaufman
Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA
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Anne K Churchland
Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA
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Anthony M Zador
Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA
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Abstract

Brain function is determined by connectivity among brain areas, and disruption of this connectivity leads to neuropsychiatric disorders. Understanding connectivity is essential to modern neuroscience, but mesoscale connectivity atlases are currently slow and expensive to generate, exist for few model systems, and require pooling across many brains. Here we present a method, muMAPseq (multisource Multiplexed Analysis of Projections by sequencing), which leverages barcoding and high-throughput sequencing to generate atlases from single animals rapidly and at low cost. We apply muMAPseq to tracing the neocortical connectome of individual mice, and demonstrate high reproducibility, and accuracy. Applying muMAPseq to the mutant BTBR mouse strain, which lacks a corpus callosum, we recapitulate its known connectopathies, and also uncover novel deficits. muMAPseq allows individual laboratories to generate atlases tailored to individuals, disease models, and new model species, and will facilitate quantitative comparative connectomics, permitting examination of how age, sex, environment, genetics and species affect neuronal wiring.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license.
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Posted September 20, 2018.
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High-throughput mapping of mesoscale connectomes in individual mice
Longwen Huang, Justus M Kebschull, Daniel Furth, Simon Musall, Matthew T Kaufman, Anne K Churchland, Anthony M Zador
bioRxiv 422477; doi: https://doi.org/10.1101/422477
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High-throughput mapping of mesoscale connectomes in individual mice
Longwen Huang, Justus M Kebschull, Daniel Furth, Simon Musall, Matthew T Kaufman, Anne K Churchland, Anthony M Zador
bioRxiv 422477; doi: https://doi.org/10.1101/422477

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