AANAT1 functions in astrocytes to regulate sleep homeostasis

  1. Sejal Davla
  2. Gregory Artiushin
  3. Yongjun Li
  4. Daryan Chitsaz
  5. Sally Li
  6. Amita Sehgal
  7. Donald J van Meyel  Is a corresponding author
  1. McGill University, Canada
  2. University of Pennsylvania, United States
  3. Howard Hughes Medical Institute, University of Pennsylvania, United States

Abstract

How the brain controls the need and acquisition of recovery sleep after prolonged wakefulness is an important issue in sleep research. The monoamines serotonin and dopamine are key regulators of sleep in mammals and in Drosophila. We found that the enzyme arylalkylamine N-acetyltransferase 1 (AANAT1) is expressed by Drosophila astrocytes and specific subsets of neurons in the adult brain. AANAT1 acetylates monoamines and inactivates them, and we found that AANAT1 limited the accumulation of serotonin and dopamine in the brain upon sleep deprivation. Loss of AANAT1 from astrocytes, but not from neurons, caused flies to increase their daytime recovery sleep following overnight sleep deprivation. Together, these findings demonstrate a crucial role for AANAT1 and astrocytes in the regulation of monoamine bioavailability and homeostatic sleep.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files.

Article and author information

Author details

  1. Sejal Davla

    Centre for Research In Neuroscience, Dept. of Neurology and Neurosurgery, McGill University, Montreal, Canada
    Competing interests
    No competing interests declared.
  2. Gregory Artiushin

    Neuroscience Graduate Group, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States
    Competing interests
    No competing interests declared.
  3. Yongjun Li

    Neuroscience Graduate Group, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States
    Competing interests
    No competing interests declared.
  4. Daryan Chitsaz

    Centre for Research In Neuroscience, Dept. of Neurology and Neurosurgery, McGill University, Montreal, Canada
    Competing interests
    No competing interests declared.
  5. Sally Li

    Centre for Research In Neuroscience, Dept. of Neurology and Neurosurgery, McGill University, Montreal, Canada
    Competing interests
    No competing interests declared.
  6. Amita Sehgal

    Neuroscience, Howard Hughes Medical Institute, University of Pennsylvania, Philadelphia, United States
    Competing interests
    Amita Sehgal, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7149-8588
  7. Donald J van Meyel

    Centre for Research In Neuroscience, Dept. of Neurology and Neurosurgery, McGill University, Montreal, Canada
    For correspondence
    don.vanmeyel@mcgill.ca
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6075-8599

Funding

Natural Sciences and Engineering Research Council of Canada (RGPIN-2017-05142)

  • Donald J van Meyel

Canadian Institutes of Health Research (MOP-137034)

  • Donald J van Meyel

National Institutes of Health (DK120757)

  • Amita Sehgal

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

Reviewing Editor

  1. K VijayRaghavan, National Centre for Biological Sciences, Tata Institute of Fundamental Research, India

Version history

  1. Received: November 27, 2019
  2. Accepted: September 18, 2020
  3. Accepted Manuscript published: September 21, 2020 (version 1)
  4. Version of Record published: October 12, 2020 (version 2)

Copyright

© 2020, Davla 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

  • 2,078
    Page views
  • 403
    Downloads
  • 20
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.

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. Sejal Davla
  2. Gregory Artiushin
  3. Yongjun Li
  4. Daryan Chitsaz
  5. Sally Li
  6. Amita Sehgal
  7. Donald J van Meyel
(2020)
AANAT1 functions in astrocytes to regulate sleep homeostasis
eLife 9:e53994.
https://doi.org/10.7554/eLife.53994

Further reading

    1. Neuroscience
    Connon I Thomas, Melissa A Ryan ... Benjamin Scholl
    Research Article

    Postsynaptic mitochondria are critical for the development, plasticity, and maintenance of synaptic inputs. However, their relationship to synaptic structure and functional activity is unknown. We examined a correlative dataset from ferret visual cortex with in vivo two-photon calcium imaging of dendritic spines during visual stimulation and electron microscopy reconstructions of spine ultrastructure, investigating mitochondrial abundance near functionally and structurally characterized spines. Surprisingly, we found no correlation to structural measures of synaptic strength. Instead, we found that mitochondria are positioned near spines with orientation preferences that are dissimilar to the somatic preference. Additionally, we found that mitochondria are positioned near groups of spines with heterogeneous orientation preferences. For a subset of spines with a mitochondrion in the head or neck, synapses were larger and exhibited greater selectivity to visual stimuli than those without a mitochondrion. Our data suggest mitochondria are not necessarily positioned to support the energy needs of strong spines, but rather support the structurally and functionally diverse inputs innervating the basal dendrites of cortical neurons.

    1. Neuroscience
    Weiwei Qui, Chelsea R Hutch ... Darleen Sandoval
    Research Article

    Several discrete groups of feeding-regulated neurons in the nucleus of the solitary tract (nucleus tractus solitarius; NTS) suppress food intake, including avoidance-promoting neurons that express Cck (NTSCck cells) and distinct Lepr- and Calcr-expressing neurons (NTSLepr and NTSCalcr cells, respectively) that suppress food intake without promoting avoidance. To test potential synergies among these cell groups we manipulated multiple NTS cell populations simultaneously. We found that activating multiple sets of NTS neurons (e.g., NTSLepr plus NTSCalcr (NTSLC), or NTSLC plus NTSCck (NTSLCK)) suppressed feeding more robustly than activating single populations. While activating groups of cells that include NTSCck neurons promoted conditioned taste avoidance (CTA), NTSLC activation produced no CTA despite abrogating feeding. Thus, the ability to promote CTA formation represents a dominant effect but activating multiple non-aversive populations augments the suppression of food intake without provoking avoidance. Furthermore, silencing multiple NTS neuron groups augmented food intake and body weight to a greater extent than silencing single populations, consistent with the notion that each of these NTS neuron populations plays crucial and cumulative roles in the control of energy balance. We found that silencing NTSLCK neurons failed to blunt the weight-loss response to vertical sleeve gastrectomy (VSG) and that feeding activated many non-NTSLCK neurons, however, suggesting that as-yet undefined NTS cell types must make additional contributions to the restraint of feeding.