insomniac links the development and function of a sleep regulatory circuit

  1. Qiuling Li
  2. Hyunsoo Jang
  3. Kayla Y Lim
  4. Alexie Lessing
  5. Nicholas Stavropoulos  Is a corresponding author
  1. New York University School of Medicine, United States

Abstract

Although many genes are known to influence sleep, when and how they impact sleep-regulatory circuits remain ill-defined. Here we show that Insomniac (Inc), a conserved adaptor for the autism-associated Cul3 ubiquitin ligase, acts in a restricted period of neuronal development to impact sleep in adult Drosophila. The loss of inc causes structural and functional alterations within the mushroom body, a center for sensory integration, associative learning, and sleep regulation. In inc mutants, mushroom body neurons are produced in excess, develop anatomical defects that impede circuit assembly, and are unable to promote sleep when activated in adulthood. Our findings link neurogenesis and postmitotic development of sleep-regulatory neurons to their adult function and suggest that developmental perturbations of circuits that couple sensory inputs and sleep may underlie sleep dysfunction in neurodevelopmental disorders.

Data availability

Data for all figures and code used to analyze sleep are included in the supporting files.

Article and author information

Author details

  1. Qiuling Li

    Department of Neuroscience and Physiology, New York University School of Medicine, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Hyunsoo Jang

    Department of Neuroscience and Physiology, New York University School of Medicine, 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:" 0000-0001-9191-3697
  3. Kayla Y Lim

    Department of Neuroscience and Physiology, New York University School of Medicine, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Alexie Lessing

    Department of Neuroscience and Physiology, New York University School of Medicine, 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:" 0000-0003-2044-7822
  5. Nicholas Stavropoulos

    Department of Neuroscience and Physiology, New York University School of Medicine, New York, United States
    For correspondence
    stavropoulos@waksman.rutgers.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5915-2760

Funding

Howard Hughes Medical Institute (International Student Research Fellowship)

  • Qiuling Li

Irma T. Hirschl Trust (Career Scientist Award)

  • Nicholas Stavropoulos

National Institute of Neurological Disorders and Stroke (R01NS112844)

  • Nicholas Stavropoulos

National Institute of Neurological Disorders and Stroke (R21NS111304)

  • Nicholas Stavropoulos

G. Harold and Leila Y. Mathers Foundation

  • Nicholas Stavropoulos

Whitehall Foundation (2013-05-78)

  • Nicholas Stavropoulos

Alfred P. Sloan Foundation

  • Nicholas Stavropoulos

Leon Levy Foundation

  • Nicholas Stavropoulos

Brain and Behavior Research Foundation (NARSAD Young Investigator)

  • Nicholas Stavropoulos

Sleep Research Society Foundation (J. Christian Gillin,M.D. Research Award)

  • Nicholas Stavropoulos

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

Reviewing Editor

  1. Ronald L Calabrese, Emory University, United States

Publication history

  1. Received: December 4, 2020
  2. Accepted: October 15, 2021
  3. Accepted Manuscript published: December 15, 2021 (version 1)
  4. Accepted Manuscript updated: December 16, 2021 (version 2)
  5. Version of Record published: January 13, 2022 (version 3)

Copyright

© 2021, Li 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. Qiuling Li
  2. Hyunsoo Jang
  3. Kayla Y Lim
  4. Alexie Lessing
  5. Nicholas Stavropoulos
(2021)
insomniac links the development and function of a sleep regulatory circuit
eLife 10:e65437.
https://doi.org/10.7554/eLife.65437
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