Cited by 45Neurobiology and Insect Physiology ResearchNeuroscience and Neuropharmacology ResearchRegulation of Appetite and Obesity

Gliotransmission of D-serine promotes thirst-directed behaviors in Drosophila

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Park, Annie, Croset, Vincent, Otto, Nils, Agarwal, Devika, Treiber, Christoph D., Meschi, Eleonora, Sims, David, Waddell, Scott·2022·Current Biology

Published version of a preprint

Abstract

Thirst emerges from a range of cellular changes that ultimately motivate an animal to consume water. Although thirst-responsive neuronal signals have been reported, the full complement of brain responses is unclear. Here, we identify molecular and cellular adaptations in the brain using single-cell sequencing of water-deprived Drosophila. Water deficiency primarily altered the glial transcriptome. Screening the regulated genes revealed astrocytic expression of the astray-encoded phosphoserine phosphatase to bi-directionally regulate water consumption. Astray synthesizes the gliotransmitter D-serine, and vesicular release from astrocytes is required for drinking. Moreover, dietary D-serine rescues aay-dependent drinking deficits while facilitating water consumption and expression of water-seeking memory. D-serine action requires binding to neuronal NMDA-type glutamate receptors. Fly astrocytes contribute processes to tripartite synapses, and the proportion of astrocytes that are themselves activated by glutamate increases with water deprivation. We propose that thirst elevates astrocytic D-serine release, which awakens quiescent glutamatergic circuits to enhance water procurement.

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Crossref · 10.1016/j.cub.2022.07.038

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  1. [24]Fischer R. Schliess F. Häussinger D. Characterization of the hypo-osmolarity-induced Ca2+ response in cultured rat astrocytes Glia 20 1997 51 58 9145304
  2. [58]Kremer M.C. Jung C. Batelli S. Rubin G.M. Gaul U. The glia of the adult Drosophila nervous system Glia 65 2017 606 638 28133822 PMC5324652
  3. [105]Huang Y. Stern M. In vivo properties of the drosophila inebriated-encoded neurotransmitter transporter J. Neurosci. 22 2002 1698 1708 11880499 PMC6758900

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Authors
Park, A., Croset, V., Otto, N., Agarwal, D., Treiber, C. D., Meschi, E., Sims, D., & Waddell, S.
Affiliations
  • University of Oxford (GB)
  • Durham University (GB)
  • John Radcliffe Hospital (GB)
Corresponding author
  • Croset, Vincent
  • Waddell, Scott
Venue
Current Biology
Publisher
Elsevier BV
Published
2022-09
Volume
32
Issue
18
Pages
3952-3970.e8
ISSN
0960-9822 (ISSN-L)
OpenAlex
W4290840293
Cited by
45
References
174
Citations by year
2026: 6 · 2025: 15 · 2024: 10 · 2023: 10 · 2022: 4
FWCI
4.31
Type
journal article
Language
en
Open access
Locations
  • Current Biology (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Durham Research Online (Durham University) (acceptedVersion, other-oa)
  • Durham Research Online (Durham University) (submittedVersion, cc-by)
Funders
  • Wellcome Trust (203261, 221300/Z/20/Z, 221300, Z/17/Z, 200846, 209235, 203261/Z/16/Z, 200846/Z/16/Z, 209235/Z/17/Z)
  • Durham University
  • National Institute of Mental Health (RF1MH117815)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurobiology and Insect Physiology Research
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
Keywords
thirst, D-serine, gliotransmission, astrocytes, phosphoserine phosphatase, water deprivation, drinking behavior, NMDA receptor, tripartite synapse, Drosophila, single-cell RNA sequencing
MeSH terms
Animals, Astrocytes, Drosophila, Synaptic Transmission, Serine, Thirst, Water, Receptors, N-Methyl-D-Aspartate, N-Methylaspartate, Receptors, Glutamate, Glutamic Acid

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