Distributed control circuits across a brain-and-cord connectome

Nature, vol. 656, pp. 957–970

Abstract

Abstract Just as genomes revolutionized molecular genetics, connectomes (maps of neurons and synapses) are transforming neuroscience. To date, the only organisms with complete connectomes are worms 1–3 , sea squirts 4 and comb jellies 5 (10 3 –10 4 synapses). By contrast, the fruit fly is more complex (10 8 synaptic connections), with a brain that supports learning and spatial memory 6,7 and an intricate ventral nerve cord analogous to the vertebrate spinal cord 8–12 . Here we report a densely reconstructed adult fly connectome that unites the brain and ventral nerve cord, and we leverage this resource to investigate principles of neural control. We show that effector neurons (motor neurons, endocrine cells and efferent neurons targeting the viscera) are primarily influenced by sensory neurons in the same body part, forming local feedback loops. These local loops are linked by long-range circuits that involve ascending and descending neurons organized into behaviour-centric modules. Single ascending and descending neurons are often positioned to influence the voluntary movements of multiple body parts, together with the endocrine cells or visceral organs that support those movements. Brain regions involved in learning and navigation supervise these circuits. These results reveal an architecture that is distributed, parallelized and embodied, reminiscent of distributed control architectures in engineered systems 13,14 .

Authors 91

1. Alexander Shakeel Bates corresponding

   Harvard University · University of Oxford

   Affiliation as printed

   Centre for Neural Circuit and Behaviour, University of Oxford, Oxford, UK. Alexander_Bates@hms.harvard.edu

   Department of Neurobiology, Harvard Medical School, Boston, MA, USA. Alexander_Bates@hms.harvard.edu

   Centre for Neural Circuit and Behaviour, Universityof Oxford, Oxford, UK

   Department of Neurobiology, Harvard Medical School, Boston, MA, USA

2. Jasper S. Phelps corresponding

   Harvard University · École Polytechnique Fédérale de Lausanne

   Affiliation as printed

   Department of Neurobiology, Harvard Medical School, Boston, MA, USA. jasper.s.phelps@gmail.com

   Neuroengineering Laboratory, Brain Mind Institute and Institute of Bioengineering, EPFL, Lausanne, Switzerland. jasper.s.phelps@gmail.com

   Department of Neurobiology, Harvard Medical School, Boston, MA, USA

   Neuroengineering Laboratory, Brain Mind Institute and Institute of Bioengineering, EPFL, Lausanne, Switzerland

3. Minsu Kim

   Harvard University

   Affiliation as printed

   Center for Brain Science, Harvard University, Cambridge, MA, USA

   Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA, USA

   Department of Neurobiology, Harvard Medical School, Boston, MA, USA

4. Helen H. Yang

   Harvard University

   Affiliation as printed

   Department of Neurobiology, Harvard Medical School, Boston, MA, USA

5. Arie Matsliah

   Princeton University

   Affiliation as printed

   Princeton Neuroscience Institute, Princeton University, Princeton, NJ, USA

6. Zaki Ajabi

   Harvard University

   Affiliation as printed

   Department of Neurobiology, Harvard Medical School, Boston, MA, USA

7. Eric Perlman
   Affiliation as printed

   Yikes, Baltimore, MD, USA

   Yikes LLC, Baltimore, MD, USA

8. Mohammed Abdal Monium Osman

   Harvard University

   Affiliation as printed

   Department of Neurobiology, Harvard Medical School, Boston, MA, USA

9. Christopher K. Salmon

   Princeton University

   Affiliation as printed

   Princeton Neuroscience Institute, Princeton University, Princeton, NJ, USA

10. Jay Gager

    Princeton University

    Affiliation as printed

    Princeton Neuroscience Institute, Princeton University, Princeton, NJ, USA

11. Benjamin Silverman

    Princeton University

    Affiliation as printed

    Princeton Neuroscience Institute, Princeton University, Princeton, NJ, USA

12. Sophia Renauld

    Harvard University

    Affiliation as printed

    Department of Neurobiology, Harvard Medical School, Boston, MA, USA

13. Farzaan Salman

    West Virginia University · Harvard University

    Affiliation as printed

    Department of Biology, West Virginia University, Morgantown, WV, USA

    Department of Neurobiology, Harvard Medical School, Boston, MA, USA

14. Matthew F. Collie

    Harvard University

    Affiliation as printed

    Department of Neurobiology, Harvard Medical School, Boston, MA, USA

15. Jingxuan Fan

    Harvard University

    Affiliation as printed

    Department of Neurobiology, Harvard Medical School, Boston, MA, USA

16. Diego A. Pacheco

    Harvard University

    Affiliation as printed

    Department of Neurobiology, Harvard Medical School, Boston, MA, USA

17. Yunzhi Zhao

    Harvard University

    Affiliation as printed

    Department of Neurobiology, Harvard Medical School, Boston, MA, USA

18. Wenyi Zhang

    Harvard University

    Affiliation as printed

    Department of Neurobiology, Harvard Medical School, Boston, MA, USA

    Aelysia LTD, Bristol, UK

19. Laia Serratosa Capdevila
    Affiliation as printed

    Aelysia, Bristol, UK

    Aelysia LTD, Bristol, UK

20. Ruairí J.V. Roberts
    Affiliation as printed

    Aelysia, Bristol, UK

    Aelysia LTD, Bristol, UK

21. Eva J Munnelly
    Affiliation as printed

    Aelysia, Bristol, UK

    Aelysia LTD, Bristol, UK

22. Nina Griggs
    Affiliation as printed

    Aelysia, Bristol, UK

    Aelysia LTD, Bristol, UK

23. Helen Langley
    Affiliation as printed

    Aelysia, Bristol, UK

    Aelysia LTD, Bristol, UK

24. Borja Moya‐Llamas

    Harvard University · Colorado College

    Affiliation as printed

    Aelysia, Bristol, UK

    Center for Brain Science, Harvard University, Cambridge, MA, USA

    Psychology Department, Colorado College, Colorado Springs, CO, USA

25. Zuoyu Zhang

    Chinese Academy of Medical Sciences & Peking Union Medical College · Princeton University · Chinese Institute for Brain Research

    Affiliation as printed

    Beijing Institute for Brain Research, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

    Chinese Institute for Brain Research, Beijing, Beijing, China

    Princeton Neuroscience Institute, Princeton University, Princeton, NJ, USA

26. Ryan T. Maloney

    Harvard University · Colorado College · Princeton University

    Affiliation as printed

    Center for Brain Science, Harvard University, Cambridge, MA, USA

    Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA, USA

    Psychology Department, Colorado College, Colorado Springs, CO, USA

    Princeton Neuroscience Institute, Princeton University, Princeton, NJ, USA

27. Szi-chieh Yu

    Princeton University

    Affiliation as printed

    Princeton Neuroscience Institute, Princeton University, Princeton, NJ, USA

28. Amy Robinson Sterling

    Princeton University

    Affiliation as printed

    Princeton Neuroscience Institute, Princeton University, Princeton, NJ, USA

    Eyewire, Boston, MA, USA

29. Marissa Sorek

    Princeton University

    Affiliation as printed

    Princeton Neuroscience Institute, Princeton University, Princeton, NJ, USA

    Eyewire, Boston, MA, USA

30. Krzysztof Kruk

    Princeton University

    Affiliation as printed

    Eyewire, Boston, MA, USA

    Princeton Neuroscience Institute, Princeton University, Princeton, NJ, USA

31. Nikitas Serafetinidis

    MRC Laboratory of Molecular Biology

    Affiliation as printed

    Eyewire, Boston, MA, USA

    Neurobiology Division, MRC Laboratory of Molecular Biology, Cambridge, UK

32. Serene Dhawan

    Princeton University · Leipzig University

    Affiliation as printed

    Princeton Neuroscience Institute, Princeton University, Princeton, NJ, USA

    Genetics Department, Leipzig University, Leipzig, Germany

33. Finja Klemm

    University of Cambridge · Leipzig University

    Affiliation as printed

    Genetics Department, Leipzig University, Leipzig, Germany

    Zoology Department, University of Cambridge, Cambridge, UK

34. Paul S Brooks

    University of Cambridge · University of Chicago

    Affiliation as printed

    Zoology Department, University of Cambridge, Cambridge, UK

    Department of Molecular Genetics and Cell Biology, The University of Chicago, Chicago, IL, USA

35. Ellen Lesser

    University of Washington · University of Chicago

    Affiliation as printed

    Department of Molecular Genetics and Cell Biology, The University of Chicago, Chicago, IL, USA

    Department of Neurobiology and Biophysics, University of Washington, Seattle, WA, USA

36. Jessica M. Jones

    University of Washington

    Affiliation as printed

    Department of Neurobiology and Biophysics, University of Washington, Seattle, WA, USA

37. Sara E. Pierce-Lundgren

    University of Washington

    Affiliation as printed

    Department of Neurobiology and Biophysics, University of Washington, Seattle, WA, USA

38. Su-Yee J. Lee

    University of Washington

    Affiliation as printed

    Department of Neurobiology and Biophysics, University of Washington, Seattle, WA, USA

39. Yichen Luo

    West Virginia University · University of Washington

    Affiliation as printed

    Department of Neurobiology and Biophysics, University of Washington, Seattle, WA, USA

    Department of Biology, West Virginia University, Morgantown, WV, USA

40. Andrew P. Cook

    University of Nevada, Reno · Virginia Tech

    Affiliation as printed

    School of Neuroscience, Virginia Tech, Blacksburg, VA, USA

    Department of Biology, University of Nevada Reno, Reno, NV, USA

41. Theresa H. McKim

    University of Nevada, Reno · Vanderbilt University

    Affiliation as printed

    Department of Biology, University of Nevada Reno, Reno, NV, USA

    Department of Biological Sciences, Vanderbilt University, Nashville, TN, USA

42. Dimitrios Stasi Giakoumas

    University of Iowa · University of Florida · Max Planck Institute for Biological Intelligence

    Affiliation as printed

    Department of Biology, University of Florida, Gainesville, FL, USA

    Interdisciplinary Graduate Program in Neuroscience, University of Iowa, Iowa City, IA, USA

    Max Planck Institute for Biological Intelligence, Martinsried, Germany

43. Benjamin Gorko

    University of California, Santa Barbara · University of Puerto Rico, Medical Sciences Campus

    Affiliation as printed

    Molecular, Cellular, and Developmental Biology, University of California Santa Barbara, Santa Barbara, CA, USA

    Institute of Neurobiology, University of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico

44. Justin Ellis-Joyce

    Howard Hughes Medical Institute · Johns Hopkins University · Princeton University

    Affiliation as printed

    Department of Neuroscience, Johns Hopkins University, Baltimore, MD, USA

    HHMI Janelia, Ashburn, VA, USA

    Princeton Neuroscience Institute, Princeton University, Princeton, NJ, USA

45. Jiayi Zhang

    Chinese Academy of Sciences · Princeton University · Center for Excellence in Brain Science and Intelligence Technology

    Affiliation as printed

    Institute of Neuroscience, Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, China

    Princeton Neuroscience Institute, Princeton University, Princeton, NJ, USA

46. Emily C. Kophs

    Vanderbilt University · Princeton University

    Affiliation as printed

    Department of Biological Sciences, Vanderbilt University, Nashville, TN, USA

    Princeton Neuroscience Institute, Princeton University, Princeton, NJ, USA

47. Tjalda Falt

    Princeton University · Max Planck Institute for Biological Intelligence

    Affiliation as printed

    Max Planck Institute for Biological Intelligence, Martinsried, Germany

    Princeton Neuroscience Institute, Princeton University, Princeton, NJ, USA

48. Alexa M. Negron-Morales

    University of Puerto Rico, Medical Sciences Campus

    Affiliation as printed

    Institute of Neurobiology, University of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico

    Zetta AI LLC, Sherrill, NY, USA

49. A Burke

    Princeton University

    Affiliation as printed

    Princeton Neuroscience Institute, Princeton University, Princeton, NJ, USA

    Zetta AI LLC, Sherrill, NY, USA

50. James Hebditch

    Princeton University

    Affiliation as printed

    Princeton Neuroscience Institute, Princeton University, Princeton, NJ, USA

    Zetta AI LLC, Sherrill, NY, USA

51. Kyle Patrick Willie

    Princeton University

    Affiliation as printed

    Princeton Neuroscience Institute, Princeton University, Princeton, NJ, USA

    Zetta AI LLC, Sherrill, NY, USA

52. Ryan Willie

    Princeton University

    Affiliation as printed

    Princeton Neuroscience Institute, Princeton University, Princeton, NJ, USA

    Zetta AI LLC, Sherrill, NY, USA

53. Nico Kemnitz
    Affiliation as printed

    Zetta AI, Sherrill, NY, USA

    Zetta AI LLC, Sherrill, NY, USA

54. Dodam Ih

    University of Edinburgh

    Affiliation as printed

    Zetta AI, Sherrill, NY, USA

    School of Informatics, University of Edinburgh, Edinburgh, UK

55. Kisuk Lee

    Japan Advanced Institute of Science and Technology

    Affiliation as printed

    Zetta AI, Sherrill, NY, USA

    Japan Advanced Institute of Science and Technology(JAIST), Nomi, Japan

56. Ran Lu

    University of Bonn

    Affiliation as printed

    Zetta AI, Sherrill, NY, USA

    Molecular Brain Physiology and Behavior, LIMES Institute, University of Bonn, Bonn, Germany

57. Akhilesh Halageri

    Princeton University

    Affiliation as printed

    Zetta AI, Sherrill, NY, USA

    Princeton Neuroscience Institute, Princeton University, Princeton, NJ, USA

58. J. Alexander Bae
    Affiliation as printed

    Zetta AI, Sherrill, NY, USA

    Eyewire, Boston, MA, USA

59. Ben Jourdan

    University of Edinburgh

    Affiliation as printed

    School of Informatics, University of Edinburgh, Edinburgh, UK

    Eyewire, Boston, MA, USA

60. Gregory Schwartzman

    Japan Advanced Institute of Science and Technology

    Affiliation as printed

    Japan Advanced Institute of Science and Technology (JAIST), Nomi, Japan

    Eyewire, Boston, MA, USA

61. Damian D. Demarest

    University of Bonn

    Affiliation as printed

    Molecular Brain Physiology and Behavior, LIMES Institute, University of Bonn, Bonn, Germany

    Eyewire, Boston, MA, USA

62. Doug Bland

    West Virginia University · Harvard University

    Affiliation as printed

    Eyewire, Boston, MA, USA

    Department of Biology, West Virginia University, Morgantown, WV, USA

    Department of Neurobiology, Harvard Medical School, Boston, MA, USA

63. Anne Kristiansen

    West Virginia University

    Affiliation as printed

    Eyewire, Boston, MA, USA

    Department of Biology, West Virginia University, Morgantown, WV, USA

64. Jaime Skelton
    Affiliation as printed

    Eyewire, Boston, MA, USA

65. Tom Stocks

    Princeton University

    Affiliation as printed

    Eyewire, Boston, MA, USA

    Princeton Neuroscience Institute, Princeton University, Princeton, NJ, USA

66. Dustin Garner

    Allen Institute for Brain Science · University of California, Santa Barbara

    Affiliation as printed

    Molecular, Cellular, and Developmental Biology, University of California Santa Barbara, Santa Barbara, CA, USA

    Allen Institute for Brain Science, Seattle, WA, USA

67. Sandeep Kumar

    Vanderbilt University · Princeton University

    Affiliation as printed

    Princeton Neuroscience Institute, Princeton University, Princeton, NJ, USA

    Department of Biological Sciences, Vanderbilt University, Nashville, TN, USA

68. Minsu Kim

    University of Bonn · Harvard University

    Affiliation as printed

    Center for Brain Science, Harvard University, Cambridge, MA, USA

    Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA, USA

    Department of Neurobiology, Harvard Medical School, Boston, MA, USA

    Molecular Brain Physiology and Behavior, LIMES Institute, University of Bonn, Bonn, Germany

69. Benjamin L. de Bivort

    Harvard University · University of Puerto Rico, Medical Sciences Campus

    Affiliation as printed

    Center for Brain Science, Harvard University, Cambridge, MA, USA

    Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA, USA

    Institute of Neurobiology, University of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico

70. Anna Verbe

    University of Puerto Rico, Medical Sciences Campus · Princeton University

    Affiliation as printed

    Princeton Neuroscience Institute, Princeton University, Princeton, NJ, USA

    Institute of Neurobiology, University of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico

71. Gabriel A. Nieves-Sanabria

    University of Puerto Rico, Medical Sciences Campus · Virginia Tech

    Affiliation as printed

    Institute of Neurobiology, University of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico

    School of Neuroscience, Virginia Tech, Blacksburg, VA, USA

72. Devon L. Jones

    University of Nevada, Reno · University of Würzburg

    Affiliation as printed

    Eyewire, Boston, MA, USA

    Department of Biochemistry and Molecular Biology, University of Nevada Reno, Reno, NV, USA

    Neurobiology and Genetics, Theodor-Boveri-Institute, Biocenter, Julius-Maximilians-University of Würzburg, Am Hubland, Würzburg, Germany

73. Zijin Huang

    Princeton University

    Affiliation as printed

    Princeton Neuroscience Institute, Princeton University, Princeton, NJ, USA

    Zetta AI LLC, Sherrill, NY, USA

74. Sofia Pinto

    Champalimaud Foundation · Howard Hughes Medical Institute

    Affiliation as printed

    Champalimaud Neuroscience Programme, Champalimaud Centre for the Unknown, Lisbon, Portugal

    HHMI Janelia, Ashburn, VA, USA

75. Celia David

    Howard Hughes Medical Institute

    Affiliation as printed

    Eyewire, Boston, MA, USA

    HHMI Janelia, Ashburn, VA, USA

76. Omaris Y. De Pablo-Crespo

    University of Puerto Rico, Medical Sciences Campus · University of Washington

    Affiliation as printed

    Institute of Neurobiology, University of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico

    Department of Neurobiology and Biophysics, University of Washington, Seattle, WA, USA

77. Wolf Huetteroth

    Princeton University · Leipzig University

    Affiliation as printed

    Department of Biology, Leipzig University, Leipzig, Germany

    Princeton Neuroscience Institute, Princeton University, Princeton, NJ, USA

78. Zequan Liu Aachen

    Harvard University · RWTH Aachen University

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    RWTH Aachen University, Aachen, Germany

    Center for Brain Science, Harvard University, Cambridge, MA, USA

79. Fernando J. Figueroa Santiago

    University of Puerto Rico, Medical Sciences Campus · Princeton University

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    Institute of Neurobiology, University of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico

    Princeton Neuroscience Institute, Princeton University, Princeton, NJ, USA

80. Kevin C. Daly

    West Virginia University · Harvard University

    Affiliation as printed

    Department of Biology, West Virginia University, Morgantown, WV, USA

    Department of Neuroscience, West Virginia University, Morgantown, WV, USA

    Department of Neurobiology, Harvard Medical School, Boston, MA, USA

81. Sven Dorkenwald

    Allen Institute for Brain Science · Harvard University

    Affiliation as printed

    Allen Institute for Brain Science, Seattle, WA, USA

    Department of Neurobiology, Harvard Medical School, Boston, MA, USA

82. Forrest Collman

    Boston Children's Hospital · Allen Institute for Brain Science · Harvard University

    Affiliation as printed

    Allen Institute for Brain Science, Seattle, WA, USA

    Department of Neurobiology, Harvard Medical School, Boston, MA, USA

    F.M. Kirby Neurobiology Center, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA

83. Marie P. Suver

    Vanderbilt University

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    Department of Biological Sciences, Vanderbilt University, Nashville, TN, USA

84. Lisa M. Fenk

    Max Planck Institute for Biological Intelligence

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    Max Planck Institute for Biological Intelligence, Martinsried, Germany

85. Michael J. Pankratz

    University of Bonn

    Affiliation as printed

    Molecular Brain Physiology and Behavior, LIMES Institute, University of Bonn, Bonn, Germany

86. Zepeng Yao

    University of Florida

    Affiliation as printed

    Department of Biology, University of Florida, Gainesville, FL, USA

    Florida Chemical Senses Institute, University of Florida, Gainesville, FL, USA

    Genetics Institute, University of Florida, Gainesville, FL, USA

    McKnight Brain Institute, University of Florida, Gainesville, FL, USA

87. Fei Wang

    Chinese Academy of Sciences · Center for Excellence in Brain Science and Intelligence Technology

    Affiliation as printed

    Institute of Neuroscience, Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, China

88. Stephen J Huston

    Columbia University

    Affiliation as printed

    Department of Neuroscience, Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY, USA

89. Tomke Stürner

    MRC Laboratory of Molecular Biology

    Affiliation as printed

    Neurobiology Division, MRC Laboratory of Molecular Biology, Cambridge, UK

90. Gregory S.X.E. Jefferis

    MRC Laboratory of Molecular Biology · University of Cambridge

    Affiliation as printed

    Neurobiology Division, MRC Laboratory of Molecular Biology, Cambridge, UK

    Zoology Department, University of Cambridge, Cambridge, UK

91. Katharina Eichler

    Leipzig University

    Affiliation as printed

    Genetics Department, Leipzig University, Leipzig, Germany