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Neuronal wiring diagram of an adult brain.

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Peer-reviewed

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Abstract

Connections between neurons can be mapped by acquiring and analysing electron microscopic brain images. In recent years, this approach has been applied to chunks of brains to reconstruct local connectivity maps that are highly informative1-6, but nevertheless inadequate for understanding brain function more globally. Here we present a neuronal wiring diagram of a whole brain containing 5 × 107 chemical synapses7 between 139,255 neurons reconstructed from an adult female Drosophila melanogaster8,9. The resource also incorporates annotations of cell classes and types, nerves, hemilineages and predictions of neurotransmitter identities10-12. Data products are available for download, programmatic access and interactive browsing and have been made interoperable with other fly data resources. We derive a projectome-a map of projections between regions-from the connectome and report on tracing of synaptic pathways and the analysis of information flow from inputs (sensory and ascending neurons) to outputs (motor, endocrine and descending neurons) across both hemispheres and between the central brain and the optic lobes. Tracing from a subset of photoreceptors to descending motor pathways illustrates how structure can uncover putative circuit mechanisms underlying sensorimotor behaviours. The technologies and open ecosystem reported here set the stage for future large-scale connectome projects in other species.

Description

Acknowledgements: The authors thank J. Wiggins, G. McGrath and D. Barlieb for computer system administration; M. Husseini for project administration; J. Maitin-Shepard for Neuroglancer; P. N. Gomez for help with GPU-cluster deployment; the management at SixEleven and Ariadne for coordination and proofreader management; and T. Sloan for creating the whole-brain renderings and videos. We thank O. Hobert, S. Cook and S. Emmons for contributing their expertise on C. elegans. M.M. and H.S.S. acknowledge support from the National Institutes of Health (NIH) BRAIN Initiative RF1 MH117815, RF1 MH129268 and U24 NS126935, from the Princeton Neuroscience Institute, as well as assistance from Google and Amazon. D.D.B. was supported by NIH NIMH BRAIN Initiative grant 1RF1MH120679-01 and a Neuronex2 award (NSF 2014862). G.S.X.E.J. and D.D.B. were supported by a Wellcome Trust Collaborative Award (203261/Z/16/Z). G.S.X.E.J. was supported by Wellcome Trust Collaborative Award 220343/Z/20/Z and a Neuronex2 award (MRC MC_EX_MR/T046279/1), and received core support from the MRC (MC-U105188491). A.L. was supported by the NSF through the Center for the Physics of Biological Function (PHY-1734030). I. Tastekin was supported with a Marie Skłodowska-Curie postdoctoral fellowship (H2020-WF-01-2018-867459 to Ibrahim Tastekin) and by the Portuguese Research Council (Grant PTDC/MED-NEU/4001/2021). A.S. and S.H. were supported by National Institute Of Neurological Disorders And Stroke of the National Institutes of Health under Award Number RF1NS121911. D. Brittain, C.S.-M. and F.C. thank the Allen Institute for Brain Science founder, P. G. Allen, for his vision, encouragement and support. This work was also supported by the Intelligence Advanced Research Projects Activity via Department of Interior/Interior Business Center contract no. D16PC0005 to H.S.S. The US Government is authorized to reproduce and distribute reprints for Governmental purposes notwithstanding any copyright annotation thereon. The views and conclusions contained herein are those of the authors and should not be interpreted as necessarily representing the official policies or endorsements, either expressed or implied, of Intelligence Advanced Research Projects Activity, Department of Interior/Interior Business Center or the US Government.

Journal Title

Nature

Conference Name

Journal ISSN

0028-0836
1476-4687

Volume Title

634

Publisher

Springer Science and Business Media LLC

Rights and licensing

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)