­­­Connectomic analysis of the Drosophila lateral neuron clock cells reveals the synaptic basis of functional pacemaker classes

  1. Orie T Shafer
  2. Gabrielle J Gutierrez
  3. Kimberly Li
  4. Amber Mildenhall
  5. Daphna Spira
  6. Jonathan Marty
  7. Aurel A Lazar
  8. Maria de la Paz Fernandez  Is a corresponding author
  1. City University of New York, United States
  2. Columbia University, United States
  3. Barnard College, United States

Abstract

The circadian clock orchestrates daily changes in physiology and behavior to ensure internal temporal order and optimal timing across the day. In animals, a central brain clock coordinates circadian rhythms throughout the body and is characterized by a remarkable robustness that depends on synaptic connections between constituent neurons. The clock neuron network of Drosophila, which shares network motifs with clock networks in the mammalian brain yet is built of many fewer neurons, offers a powerful model for understanding the network properties of circadian timekeeping. Here we report an assessment of synaptic connectivity within a clock network, focusing on the critical lateral neuron (LN) clock neuron classes within the Janelia hemibrain dataset. Our results reveal that previously identified anatomical and functional subclasses of LNs represent distinct connectomic types. Moreover, we identify a small number of non-clock cell subtypes representing highly synaptically coupled nodes within the clock neuron network. This suggests that neurons lacking molecular timekeeping likely play integral roles within the circadian timekeeping network. To our knowledge, this represents the first comprehensive connectomic analysis of a circadian neuronal network.

Data availability

The current manuscript is a computational study, so no data have been generated for this manuscript. The dataset used was generated by Janelia Research Campus (Drosophila hemibrain connectome) and it is publicly available: https://neuprint.janelia.org/The original manuscript (Scheffer et al., 2020) can be found here:https://doi.org/10.7554/eLife.57443

The following previously published data sets were used
    1. Louis K Scheffer
    2. C Shan Xu
    3. Michal Januszewski
    4. Zhiyuan Lu
    5. Shin-ya Takemura
    6. Kenneth J Hayworth
    7. Gary B Huang
    8. Kazunori Shinomiya
    9. Jeremy Maitlin-Shepard
    10. Stuart Berg
    11. Jody Clements
    12. Philip M Hubbard
    13. William T Katz
    14. Lowell Umayam
    15. Ting Zhao
    16. David Ackerman
    17. Tim Blakely
    18. John Bogovic
    19. Tom Dolafi
    20. Dagmar Kainmueller
    21. Takashi Kawase
    22. Khaled A Khairy
    23. Laramie Leavitt
    24. Peter H Li
    25. Larry Lindsey
    26. Nicole Neubarth
    27. Donald J Olbris
    28. Hideo Otsuna
    29. Eric T Trautman
    30. Masayoshi Ito
    31. Alexander S Bates
    32. Jens Goldammer
    33. Tanya Wolff
    34. Robert Svirskas
    35. Philipp Schlegel
    36. Erika Neace
    37. Christopher J Knecht
    38. Chelsea X Alvarado
    39. Dennis A Bailey
    40. Samantha Ballinger
    41. Jolanta A Borycz
    42. Brandon S Canino
    43. Natasha Cheatham
    44. Michael Cook
    45. Marisa Dreher
    46. Octave Duclos
    47. Bryon Eubanks
    48. Kelli Fairbanks
    49. Samantha Finley
    50. Nora Forknall
    51. Audrey Francis
    52. Gary Patrick Hopkins
    53. Emily M Joyce
    54. SungJin Kim
    55. Nicole A Kirk
    56. Julie Kovalyak
    57. Shirley A Lauchie
    58. Alanna Lohff
    59. Charli Maldonado
    60. Emily A Manley
    61. Sari McLin
    62. Caroline Mooney
    63. Miatta Ndama
    64. Omotara Ogundeyi
    65. Nneoma Okeoma
    66. Christopher Ordish
    67. Nicholas Padilla
    68. Christopher M Patrick
    69. Tyler Paterson
    70. Elliott E Phillips
    71. Emily M Phillips
    72. Neha Rampally
    73. Caitlin Ribeiro
    74. Madelaine K Robertson
    75. Jon Thomson Rymer
    76. Sean M Ryan
    77. Megan Sammons
    78. Anne K Scott
    79. Ashley L Scott
    80. Aya Shinomiya
    81. Claire Smith
    82. Kelsey Smith
    83. Natalie L Smith
    84. Margaret A Sobeski
    85. Alia Suleiman
    86. Jackie Swift
    87. Satoko Takemura
    88. Iris Talebi
    89. Dorota Tarnogorska
    90. Emily Tenshaw
    91. Temour Tokhi
    92. John J Walsh
    93. Tansy Yang
    94. Jane Anne Horne
    95. Feng Li
    96. Ruchi Parekh
    97. Patricia K Rivlin
    98. Vivek Jayaraman
    99. Marta Costa
    100. Gregory SXE Jefferis
    101. Kei Ito
    102. Stephan Saalfeld
    103. Reed George
    104. Ian A Meinertzhagen
    105. Gerald M Rubin
    106. Harald F Hess
    107. Viren Jain
    108. Stephen M Plaza
    (2020) Resource Collection for a Connectome and Analysis of the Adult Drosophila Central Brain
    Hemibrain dataset v1.2.1.

Article and author information

Author details

  1. Orie T Shafer

    Advanced Science Research Center, City University of New York, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7177-743X
  2. Gabrielle J Gutierrez

    Center for Theoretical Neuroscience, Columbia University, New York City, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2350-1559
  3. Kimberly Li

    Department of Neuroscience and Behavior, Barnard College, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Amber Mildenhall

    Department of Neuroscience and Behavior, Barnard College, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6495-8734
  5. Daphna Spira

    Center for Theoretical Neuroscience, Columbia University, New York City, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Jonathan Marty

    Department of Electrical Engineering, Columbia University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Aurel A Lazar

    Department of Electrical Engineering, Columbia University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4261-8709
  8. Maria de la Paz Fernandez

    Department of Neuroscience and Behavior, Barnard College, NYC, United States
    For correspondence
    mfernand@barnard.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9261-6114

Funding

National Institute of Neurological Disorders and Stroke (R01NS118012)

  • Orie T Shafer
  • Maria de la Paz Fernandez

National Institutes of Health (R01NS077933)

  • Orie T Shafer

National Institutes of Health (K22 NS104187)

  • Gabrielle J Gutierrez

National Science Foundation (NeuroNex Award DBI-1707398)

  • Gabrielle J Gutierrez

Gatsby Charitable Foundation (Research Award)

  • Gabrielle J Gutierrez

National Science Foundation (Grant #2024607)

  • Aurel A Lazar

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Claude Desplan, New York University, United States

Version history

  1. Preprint posted: March 4, 2022 (view preprint)
  2. Received: March 31, 2022
  3. Accepted: June 29, 2022
  4. Accepted Manuscript published: June 29, 2022 (version 1)
  5. Accepted Manuscript updated: July 1, 2022 (version 2)
  6. Version of Record published: August 10, 2022 (version 3)

Copyright

© 2022, Shafer et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Orie T Shafer
  2. Gabrielle J Gutierrez
  3. Kimberly Li
  4. Amber Mildenhall
  5. Daphna Spira
  6. Jonathan Marty
  7. Aurel A Lazar
  8. Maria de la Paz Fernandez
(2022)
­­­Connectomic analysis of the Drosophila lateral neuron clock cells reveals the synaptic basis of functional pacemaker classes
eLife 11:e79139.
https://doi.org/10.7554/eLife.79139

Share this article

https://doi.org/10.7554/eLife.79139

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