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Connectome-constrained deep mechanistic networks predict neural responses across the fly visual system at single-neuron resolution

View ORCID ProfileJanne K. Lappalainen, View ORCID ProfileFabian D. Tschopp, View ORCID ProfileSridhama Prakhya, View ORCID ProfileMason McGill, View ORCID ProfileAljoscha Nern, View ORCID ProfileKazunori Shinomiya, View ORCID ProfileShin-ya Takemura, View ORCID ProfileEyal Gruntman, View ORCID ProfileJakob H. Macke, View ORCID ProfileSrinivas C. Turaga
doi: https://doi.org/10.1101/2023.03.11.532232
Janne K. Lappalainen
1Machine Learning in Science, Tübingen University and Tübingen AI Center, Germany
2HHMI Janelia Research Campus, Ashburn, VA, USA
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Fabian D. Tschopp
2HHMI Janelia Research Campus, Ashburn, VA, USA
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Sridhama Prakhya
2HHMI Janelia Research Campus, Ashburn, VA, USA
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Mason McGill
2HHMI Janelia Research Campus, Ashburn, VA, USA
3Computation and Neural Systems, California Institute of Technology, Pasadena, CA, USA
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Aljoscha Nern
2HHMI Janelia Research Campus, Ashburn, VA, USA
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Kazunori Shinomiya
2HHMI Janelia Research Campus, Ashburn, VA, USA
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Shin-ya Takemura
2HHMI Janelia Research Campus, Ashburn, VA, USA
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Eyal Gruntman
2HHMI Janelia Research Campus, Ashburn, VA, USA
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Jakob H. Macke
1Machine Learning in Science, Tübingen University and Tübingen AI Center, Germany
4Max Planck Institute for Intelligent Systems, Tübingen, Germany
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Srinivas C. Turaga
2HHMI Janelia Research Campus, Ashburn, VA, USA
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  • For correspondence: turagas@janelia.hhmi.org
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Abstract

We can now measure the connectivity of every neuron in a neural circuit, but we are still blind to other biological details, including the dynamical characteristics of each neuron. The degree to which connectivity measurements alone can inform understanding of neural computation is an open question. Here we show that with only measurements of the connectivity of a biological neural network, we can predict the neural activity underlying neural computation. We constructed a model neural network with the experimentally determined connectivity for 64 cell types in the motion pathways of the fruit fly optic lobe but with unknown parameters for the single neuron and single synapse properties. We then optimized the values of these unknown parameters using techniques from deep learning, to allow the model network to detect visual motion. Our mechanistic model makes detailed experimentally testable predictions for each neuron in the connectome. We found that model predictions agreed with experimental measurements of neural activity across 24 studies. Our work demonstrates a strategy for generating detailed hypotheses about the mechanisms of neural circuit function from connectivity measurements. We show that this strategy is more likely to be successful when neurons are sparsely connected—a universally observed feature of biological neural networks across species and brain regions.

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 4.0 International license.
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Posted March 13, 2023.
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Connectome-constrained deep mechanistic networks predict neural responses across the fly visual system at single-neuron resolution
Janne K. Lappalainen, Fabian D. Tschopp, Sridhama Prakhya, Mason McGill, Aljoscha Nern, Kazunori Shinomiya, Shin-ya Takemura, Eyal Gruntman, Jakob H. Macke, Srinivas C. Turaga
bioRxiv 2023.03.11.532232; doi: https://doi.org/10.1101/2023.03.11.532232
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Connectome-constrained deep mechanistic networks predict neural responses across the fly visual system at single-neuron resolution
Janne K. Lappalainen, Fabian D. Tschopp, Sridhama Prakhya, Mason McGill, Aljoscha Nern, Kazunori Shinomiya, Shin-ya Takemura, Eyal Gruntman, Jakob H. Macke, Srinivas C. Turaga
bioRxiv 2023.03.11.532232; doi: https://doi.org/10.1101/2023.03.11.532232

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