Abstract

Homeostatic and circadian processes collaborate to appropriately time and consolidate sleep and wake. To understand how these processes are integrated, we scheduled brief sleep deprivation at different times of day in Drosophila and find elevated morning rebound compared to evening. These effects depend on discrete morning and evening clock neurons, independent of their roles in circadian locomotor activity. In the R5 ellipsoid body sleep homeostat, we identified elevated morning expression of activity dependent and presynaptic gene expression as well as the presynaptic protein BRUCHPILOT consistent with regulation by clock circuits. These neurons also display elevated calcium levels in response to sleep loss in the morning, but not the evening consistent with the observed time-dependent sleep rebound. These studies reveal the circuit and molecular mechanisms by which discrete circadian clock neurons program a homeostatic sleep center.

Data availability

Sequencing data have been deposited in GEO under accession code GSE186076

The following data sets were generated

Article and author information

Author details

  1. Tomas Andreani

    Department of Neurobiology, Northwestern University, Evanston, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2967-9689
  2. Clark Rosensweig

    Department of Neurobiology, Northwestern University, Evanston, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Shiju Sisobhan

    Department of Neurobiology, Northwestern University, Evanston, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9715-1029
  4. Emmanuel Ogunlana

    Department of Neurobiology, Northwestern University, Evanston, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7955-4115
  5. William Kath

    Department of Engineering Sciences and Applied Mathematics, Northwestern University, Evanston, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Ravi Allada

    Department of Neurobiology, Northwestern University, Chicago, United States
    For correspondence
    r-allada@northwestern.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4371-1577

Funding

National Institutes of Health (R01NS106955)

  • Ravi Allada

Army Research Office (W911NF1610584)

  • Ravi Allada

National Science Foundation (DMS-1764421)

  • William Kath
  • Ravi Allada

Simons Foundation (597491-RWC)

  • William Kath
  • Ravi Allada

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

Reviewing Editor

  1. Amita Sehgal, Howard Hughes Medical Institute and Chronobiology and Sleep Institute, Perelman School of Medicine, University of Pennsylvania, United States

Version history

  1. Received: September 29, 2021
  2. Preprint posted: October 23, 2021 (view preprint)
  3. Accepted: June 23, 2022
  4. Accepted Manuscript published: June 23, 2022 (version 1)
  5. Version of Record published: July 8, 2022 (version 2)

Copyright

© 2022, Andreani 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.

Metrics

  • 2,072
    views
  • 477
    downloads
  • 13
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Tomas Andreani
  2. Clark Rosensweig
  3. Shiju Sisobhan
  4. Emmanuel Ogunlana
  5. William Kath
  6. Ravi Allada
(2022)
Circadian programming of the ellipsoid body sleep homeostat in Drosophila
eLife 11:e74327.
https://doi.org/10.7554/eLife.74327

Share this article

https://doi.org/10.7554/eLife.74327

Further reading

    1. Genetics and Genomics
    2. Neuroscience
    Donghui Yan, Bowen Hu ... Qiongshi Lu
    Research Article

    Rich data from large biobanks, coupled with increasingly accessible association statistics from genome-wide association studies (GWAS), provide great opportunities to dissect the complex relationships among human traits and diseases. We introduce BADGERS, a powerful method to perform polygenic score-based biobank-wide association scans. Compared to traditional approaches, BADGERS uses GWAS summary statistics as input and does not require multiple traits to be measured in the same cohort. We applied BADGERS to two independent datasets for late-onset Alzheimer’s disease (AD; n=61,212). Among 1738 traits in the UK biobank, we identified 48 significant associations for AD. Family history, high cholesterol, and numerous traits related to intelligence and education showed strong and independent associations with AD. Furthermore, we identified 41 significant associations for a variety of AD endophenotypes. While family history and high cholesterol were strongly associated with AD subgroups and pathologies, only intelligence and education-related traits predicted pre-clinical cognitive phenotypes. These results provide novel insights into the distinct biological processes underlying various risk factors for AD.

    1. Genetics and Genomics
    2. Microbiology and Infectious Disease
    Jason E Stajich, Brian Lovett ... Carolyn Elya
    Research Article

    Despite over a century of observations, the obligate insect parasites within the order Entomophthorales remain poorly characterized at the genetic level. In this manuscript, we present a genome for a laboratory-tractable Entomophthora muscae isolate that infects fruit flies. Our E. muscae assembly is 1.03 Gb, consists of 7810 contigs and contains 81.3% complete fungal BUSCOs. Using a comparative approach with recent datasets from entomophthoralean fungi, we show that giant genomes are the norm within Entomophthoraceae owing to extensive, but not recent, Ty3 retrotransposon activity. In addition, we find that E. muscae and its closest allies possess genes that are likely homologs to the blue-light sensor white-collar 1, a Neurospora crassa gene that has a well-established role in maintaining circadian rhythms. We uncover evidence that E. muscae diverged from other entomophthoralean fungi by expansion of existing families, rather than loss of particular domains, and possesses a potentially unique suite of secreted catabolic enzymes, consistent with E. muscae’s species-specific, biotrophic lifestyle. Finally, we offer a head-to-head comparison of morphological and molecular data for species within the E. muscae species complex that support the need for taxonomic revision within this group. Altogether, we provide a genetic and molecular foundation that we hope will provide a platform for the continued study of the unique biology of entomophthoralean fungi.