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A Drosophila computational brain model reveals sensorimotor processing.

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Peer-reviewed

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Abstract

The recent assembly of the adult Drosophila melanogaster central brain connectome, containing more than 125,000 neurons and 50 million synaptic connections, provides a template for examining sensory processing throughout the brain1,2. Here we create a leaky integrate-and-fire computational model of the entire Drosophila brain, on the basis of neural connectivity and neurotransmitter identity3, to study circuit properties of feeding and grooming behaviours. 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 initiation4. In addition, using the model to activate neurons in the feeding region of the Drosophila brain predicts those that elicit motor neuron firing5-a testable hypothesis that we validate by optogenetic activation and behavioural studies. Activating different classes of gustatory neurons in the model makes accurate predictions of how several taste modalities interact, providing circuit-level insight into aversive and appetitive taste processing. 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, and accurately describes the circuit response upon activation of different mechanosensory subtypes6-10. Our results demonstrate that modelling brain circuits using only synapse-level connectivity and predicted neurotransmitter identity generates experimentally testable hypotheses and can describe complete sensorimotor transformations.

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Acknowledgements: We thank members of the Scott laboratory for their contributions to the experimental and model design, data analysis and manuscript preparation. We thank C. Liu, M. Levy and G. Agarwal for their feedback on the initial development of the computational model. We thank the laboratories of C. Ribeiro and R. Wilson for Flywire proofreading contributions. We thank the entire Flywire community for their contributions to the proofreading of the Drosophila connectome. We thank M. Sorek for assistance with Flywire community management. We thank R. Lu, T. Macrina, K. Lee, J. A. Bae, S. Mu, B. Nehoran, E. Mitchell, S. Popovych, J. Wu, Z. Jia, M. Castro, N. Kemnitz and D. Ih for alignment and segmentation of the FAFB electron microscopy volume and registration to the original FAFB electron microscopy dataset. We thank D. Bock and E. Perlman for sponsorship of partial proofreading and registration service. We thank F. Collman, C. Schneider-Mizell, C. Jordan, D. Brittain and A. Haligeri for CAVE development and maintenance. We thank K. Kuehner, O. Ogedengbe, J. Gager, W. Silversmith and R. Morey for Neuroglancer development, tools and Codex development. We thank S. Seung for his suggestions and contributions to Flywire. N.S. is funded by the Carl Angus DeSantis Foundation. This work was supported by National Institutes of Health (NIH) awards R01DC013280 (K.S.), NIH F32DK117671 (G.R.S.), NIH F32DC018225 (P.S.) and RF1NS121911 (S.H. and A.M.S.). Flywire is supported by NIH BRAIN Initiative grants MH117815 and NS126935 to M.M. and S. Seung. Additional proofreading and infrastructure was supported by Wellcome awards 203261/Z/16/Z and 220343/Z/20/Z to G.S.X.E.J., and NIMH BRAIN Initiative award 1RF1MH120679-01 and NSF NeuroNex award DBI-2014862 to D. Bock and G.S.X.E.J. The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

Journal Title

Nature

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Journal ISSN

0028-0836
1476-4687

Volume Title

634

Publisher

Springer Nature

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Except where otherwised noted, this item's license is described as http://creativecommons.org/licenses/by/4.0/
Sponsorship
Wellcome Trust (203261/Z/16/Z)
Wellcome Trust (220343/Z/20/Z)

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