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A leaky integrate-and-fire computational model based on the connectome of the entire adult Drosophila brain reveals insights into sensorimotor processing

View ORCID ProfilePhilip K. Shiu, View ORCID ProfileGabriella R. Sterne, View ORCID ProfileNico Spiller, Romain Franconville, Andrea Sandoval, Joie Zhou, Neha Simha, View ORCID ProfileChan Hyuk Kang, View ORCID ProfileSeongbong Yu, View ORCID ProfileJinseop S. Kim, View ORCID ProfileSven Dorkenwald, Arie Matsliah, View ORCID ProfilePhilipp Schlegel, Szi-chieh Yu, View ORCID ProfileClaire E. McKellar, Amy Sterling, View ORCID ProfileMarta Costa, View ORCID ProfileKatharina Eichler, View ORCID ProfileGregory S.X.E. Jefferis, View ORCID ProfileMala Murthy, View ORCID ProfileAlexander Shakeel Bates, View ORCID ProfileNils Eckstein, View ORCID ProfileJan Funke, View ORCID ProfileSalil S. Bidaye, View ORCID ProfileStefanie Hampel, View ORCID ProfileAndrew M. Seeds, View ORCID ProfileKristin Scott
doi: https://doi.org/10.1101/2023.05.02.539144
Philip K. Shiu
1Department of Molecular and Cell Biology and Helen Wills Neuroscience Institute, University of California, Berkeley, CA, USA
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  • For correspondence: philshiu@gmail.com kscott@berkeley.edu
Gabriella R. Sterne
1Department of Molecular and Cell Biology and Helen Wills Neuroscience Institute, University of California, Berkeley, CA, USA
2University of Rochester Medical Center, Department of Biomedical Genetics
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Nico Spiller
3Max Planck Florida Institute for Neuroscience, Jupiter, FL, USA
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Romain Franconville
4HHMI Janelia Research Campus, Ashburn, USA
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Andrea Sandoval
1Department of Molecular and Cell Biology and Helen Wills Neuroscience Institute, University of California, Berkeley, CA, USA
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Joie Zhou
1Department of Molecular and Cell Biology and Helen Wills Neuroscience Institute, University of California, Berkeley, CA, USA
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Neha Simha
1Department of Molecular and Cell Biology and Helen Wills Neuroscience Institute, University of California, Berkeley, CA, USA
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Chan Hyuk Kang
5Department of Biological Sciences, Sungkyunkwan University, Suwon, 16419, South Korea
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Seongbong Yu
5Department of Biological Sciences, Sungkyunkwan University, Suwon, 16419, South Korea
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Jinseop S. Kim
5Department of Biological Sciences, Sungkyunkwan University, Suwon, 16419, South Korea
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Sven Dorkenwald
6Princeton Neuroscience Institute, Princeton University, Princeton, NJ, USA
7Computer Science Department, Princeton University, Princeton, NJ, USA
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Arie Matsliah
6Princeton Neuroscience Institute, Princeton University, Princeton, NJ, USA
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Philipp Schlegel
8Department of Zoology, University of Cambridge
9Neurobiology Division, MRC Laboratory of Molecular Biology, Cambridge
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Szi-chieh Yu
6Princeton Neuroscience Institute, Princeton University, Princeton, NJ, USA
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Claire E. McKellar
6Princeton Neuroscience Institute, Princeton University, Princeton, NJ, USA
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Amy Sterling
6Princeton Neuroscience Institute, Princeton University, Princeton, NJ, USA
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Marta Costa
8Department of Zoology, University of Cambridge
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Katharina Eichler
8Department of Zoology, University of Cambridge
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Gregory S.X.E. Jefferis
8Department of Zoology, University of Cambridge
9Neurobiology Division, MRC Laboratory of Molecular Biology, Cambridge
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Mala Murthy
6Princeton Neuroscience Institute, Princeton University, Princeton, NJ, USA
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Alexander Shakeel Bates
9Neurobiology Division, MRC Laboratory of Molecular Biology, Cambridge
10Centre for Neural Circuits and Behaviour, The University of Oxford
11Department of Neurobiology and Howard Hughes Medical Institute, Harvard Medical School, Boston, MA, USA
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Nils Eckstein
4HHMI Janelia Research Campus, Ashburn, USA
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Jan Funke
4HHMI Janelia Research Campus, Ashburn, USA
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Salil S. Bidaye
3Max Planck Florida Institute for Neuroscience, Jupiter, FL, USA
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Stefanie Hampel
12Institute of Neurobiology, University of Puerto Rico-Medical Sciences Campus, San Juan, Puerto Rico
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Andrew M. Seeds
12Institute of Neurobiology, University of Puerto Rico-Medical Sciences Campus, San Juan, Puerto Rico
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Kristin Scott
1Department of Molecular and Cell Biology and Helen Wills Neuroscience Institute, University of California, Berkeley, CA, USA
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  • ORCID record for Kristin Scott
  • For correspondence: philshiu@gmail.com kscott@berkeley.edu
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Abstract

The forthcoming assembly of the adult Drosophila melanogaster central brain connectome, containing over 125,000 neurons and 50 million synaptic connections, provides a template for examining sensory processing throughout the brain. Here, we create a leaky integrate-and-fire computational model of the entire Drosophila brain, based on neural connectivity and neurotransmitter identity, to study circuit properties of feeding and grooming behaviors. We show that activation of sugar-sensing or water-sensing gustatory neurons in the computational model accurately predicts neurons that respond to tastes and are required for feeding initiation. Computational activation of neurons in the feeding region of the Drosophila brain predicts those that elicit motor neuron firing, a testable hypothesis that we validate by optogenetic activation and behavioral studies. Moreover, computational activation of different classes of gustatory neurons makes accurate predictions of how multiple taste modalities interact, providing circuit-level insight into aversive and appetitive taste processing. Our computational model predicts that the sugar and water pathways form a partially shared appetitive feeding initiation pathway, which our calcium imaging and behavioral experiments confirm. Additionally, we applied this model to mechanosensory circuits and found that computational activation of mechanosensory neurons predicts activation of a small set of neurons comprising the antennal grooming circuit that do not overlap with gustatory circuits, and accurately describes the circuit response upon activation of different mechanosensory subtypes. Our results demonstrate that modeling brain circuits purely from connectivity and predicted neurotransmitter identity generates experimentally testable hypotheses and can accurately describe complete sensorimotor transformations.

Competing Interest Statement

The authors have declared no competing interest.

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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-ND 4.0 International license.
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Posted May 02, 2023.
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A leaky integrate-and-fire computational model based on the connectome of the entire adult Drosophila brain reveals insights into sensorimotor processing
Philip K. Shiu, Gabriella R. Sterne, Nico Spiller, Romain Franconville, Andrea Sandoval, Joie Zhou, Neha Simha, Chan Hyuk Kang, Seongbong Yu, Jinseop S. Kim, Sven Dorkenwald, Arie Matsliah, Philipp Schlegel, Szi-chieh Yu, Claire E. McKellar, Amy Sterling, Marta Costa, Katharina Eichler, Gregory S.X.E. Jefferis, Mala Murthy, Alexander Shakeel Bates, Nils Eckstein, Jan Funke, Salil S. Bidaye, Stefanie Hampel, Andrew M. Seeds, Kristin Scott
bioRxiv 2023.05.02.539144; doi: https://doi.org/10.1101/2023.05.02.539144
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A leaky integrate-and-fire computational model based on the connectome of the entire adult Drosophila brain reveals insights into sensorimotor processing
Philip K. Shiu, Gabriella R. Sterne, Nico Spiller, Romain Franconville, Andrea Sandoval, Joie Zhou, Neha Simha, Chan Hyuk Kang, Seongbong Yu, Jinseop S. Kim, Sven Dorkenwald, Arie Matsliah, Philipp Schlegel, Szi-chieh Yu, Claire E. McKellar, Amy Sterling, Marta Costa, Katharina Eichler, Gregory S.X.E. Jefferis, Mala Murthy, Alexander Shakeel Bates, Nils Eckstein, Jan Funke, Salil S. Bidaye, Stefanie Hampel, Andrew M. Seeds, Kristin Scott
bioRxiv 2023.05.02.539144; doi: https://doi.org/10.1101/2023.05.02.539144

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