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Neurotransmitter Classification from Electron Microscopy Images at Synaptic Sites in Drosophila Melanogaster

View ORCID ProfileNils Eckstein, View ORCID ProfileAlexander Shakeel Bates, Andrew Champion, Michelle Du, View ORCID ProfileYijie Yin, Philipp Schlegel, Alicia Kun-Yang Lu, Thomson Rymer, Samantha Finley-May, Tyler Paterson, View ORCID ProfileRuchi Parekh, View ORCID ProfileSven Dorkenwald, Arie Matsliah, Szi-Chieh Yu, View ORCID ProfileClaire McKellar, Amy Sterling, View ORCID ProfileKatharina Eichler, View ORCID ProfileMarta Costa, View ORCID ProfileSebastian Seung, View ORCID ProfileMala Murthy, View ORCID ProfileVolker Hartenstein, View ORCID ProfileGregory S.X.E. Jefferis, View ORCID ProfileJan Funke
doi: https://doi.org/10.1101/2020.06.12.148775
Nils Eckstein
1HHMI Janelia Research Campus, Ashburn, VA, USA
2Institute of Neuroinformatics UZH/ETHZ, Zurich, Switzerland
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Alexander Shakeel Bates
3Neurobiology Division, MRC Laboratory of Molecular Biology, Cambridge, United Kingdom
4Centre for Neural Circuits and Behaviour, The University of Oxford, Tinsley Building, Mansfield Road, Oxford OX1 3SR, United Kingdom
5Department of Neurobiology and Howard Hughes Medical Institute, Harvard Medical School, Boston, MA, USA
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Andrew Champion
6Drosophila Connectomics Group, Department of Zoology, University of Cambridge, Cambridge, United Kingdom
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Michelle Du
1HHMI Janelia Research Campus, Ashburn, VA, USA
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Yijie Yin
6Drosophila Connectomics Group, Department of Zoology, University of Cambridge, Cambridge, United Kingdom
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Philipp Schlegel
6Drosophila Connectomics Group, Department of Zoology, University of Cambridge, Cambridge, United Kingdom
3Neurobiology Division, MRC Laboratory of Molecular Biology, Cambridge, United Kingdom
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Alicia Kun-Yang Lu
1HHMI Janelia Research Campus, Ashburn, VA, USA
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Thomson Rymer
1HHMI Janelia Research Campus, Ashburn, VA, USA
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Samantha Finley-May
1HHMI Janelia Research Campus, Ashburn, VA, USA
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Tyler Paterson
1HHMI Janelia Research Campus, Ashburn, VA, USA
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Ruchi Parekh
1HHMI Janelia Research Campus, Ashburn, VA, USA
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Sven Dorkenwald
7Princeton Neuroscience Institute, Princeton University, Princeton, NJ, USA
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Arie Matsliah
7Princeton Neuroscience Institute, Princeton University, Princeton, NJ, USA
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Szi-Chieh Yu
7Princeton Neuroscience Institute, Princeton University, Princeton, NJ, USA
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Claire McKellar
7Princeton Neuroscience Institute, Princeton University, Princeton, NJ, USA
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Amy Sterling
7Princeton Neuroscience Institute, Princeton University, Princeton, NJ, USA
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Katharina Eichler
6Drosophila Connectomics Group, Department of Zoology, University of Cambridge, Cambridge, United Kingdom
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Marta Costa
6Drosophila Connectomics Group, Department of Zoology, University of Cambridge, Cambridge, United Kingdom
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Sebastian Seung
7Princeton Neuroscience Institute, Princeton University, Princeton, NJ, USA
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Mala Murthy
7Princeton Neuroscience Institute, Princeton University, Princeton, NJ, USA
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Volker Hartenstein
8Department of Molecular Cell and Developmental Biology, University of California Los Angeles, Los Angeles, USA
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Gregory S.X.E. Jefferis
3Neurobiology Division, MRC Laboratory of Molecular Biology, Cambridge, United Kingdom
6Drosophila Connectomics Group, Department of Zoology, University of Cambridge, Cambridge, United Kingdom
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Jan Funke
1HHMI Janelia Research Campus, Ashburn, VA, USA
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  • For correspondence: funkej@janelia.hhmi.org
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Abstract

High-resolution electron microscopy of nervous systems enables the reconstruction of connectomes. A key piece of missing information from connectomes is the synaptic sign. We show that for D. melanogaster, artificial neural networks can predict the transmitter type released at synapses from electron micrographs and thus add putative signs to connections. Our network discriminates between six transmitters (acetylcholine, glutamate, GABA, serotonin, dopamine, octopamine) with an average accuracy of 87%/94% for synapses/entire neurons. We developed an explainability method to reveal which features our network is using and found significant ultrastructural differences between the classical transmitters. We predict transmitters in two connectomes and characterize morphological and connection properties of tens of thousands of neurons classed by predicted transmitter expression. We find that hemilineages in D. melanogaster largely express only one fastacting transmitter among their neurons. Furthermore, we show that neurons with different transmitters may differ in features like polarization and projection targets.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • Complete revision of the manuscript.

Copyright 
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-ND 4.0 International license.
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Neurotransmitter Classification from Electron Microscopy Images at Synaptic Sites in Drosophila Melanogaster
Nils Eckstein, Alexander Shakeel Bates, Andrew Champion, Michelle Du, Yijie Yin, Philipp Schlegel, Alicia Kun-Yang Lu, Thomson Rymer, Samantha Finley-May, Tyler Paterson, Ruchi Parekh, Sven Dorkenwald, Arie Matsliah, Szi-Chieh Yu, Claire McKellar, Amy Sterling, Katharina Eichler, Marta Costa, Sebastian Seung, Mala Murthy, Volker Hartenstein, Gregory S.X.E. Jefferis, Jan Funke
bioRxiv 2020.06.12.148775; doi: https://doi.org/10.1101/2020.06.12.148775
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Neurotransmitter Classification from Electron Microscopy Images at Synaptic Sites in Drosophila Melanogaster
Nils Eckstein, Alexander Shakeel Bates, Andrew Champion, Michelle Du, Yijie Yin, Philipp Schlegel, Alicia Kun-Yang Lu, Thomson Rymer, Samantha Finley-May, Tyler Paterson, Ruchi Parekh, Sven Dorkenwald, Arie Matsliah, Szi-Chieh Yu, Claire McKellar, Amy Sterling, Katharina Eichler, Marta Costa, Sebastian Seung, Mala Murthy, Volker Hartenstein, Gregory S.X.E. Jefferis, Jan Funke
bioRxiv 2020.06.12.148775; doi: https://doi.org/10.1101/2020.06.12.148775

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