Gliotransmission of D-serine promotes thirst-directed behaviors in Drosophila
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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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∼80% of neurons in the central brain express RNA transcripts for GluClAlpha as well as at least one excitatory ionotropic glutamate receptor.
“We calculated from single-cell RNA sequencing118 that ∼80% of neurons in the central brain express RNA transcripts for GluClAlpha as well as at least one excitatory ionotropic glutamate receptor.”
From Neurotransmitter classification from electron microscopy images at synaptic sites in Drosophila melanogaster (2024) · cites this paper as [118]
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Self-citationA LAT1-Like Amino Acid Transporter Regulates Neuronal Activity in the Drosophila Mushroom Bodies
Delescluse, J., Simonnet, M. M., Ziegler, A. B., Piffaretti, K., Alves, G., Grosjean, Y., & Manière, G. (2024) · Cells · doi:10.3390/cells13161340 · Cited by 4 · see citing works
Molecular profiling of invertebrate glia
Purice, M. D., Lago‐Baldaia, I., Fernandes, V. M., & Singhvi, A. (2024) · Glia · doi:10.1002/glia.24623 · Cited by 3 · see citing works
A Role for Exaptation in Sculpting Sexually Dimorphic Brains from Shared Neural LineagesPreprint
Allen, A. M., Neville, M. C., Nojima, T., Alejevski, F., & Goodwin, S. F. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.06.04.657833 · Cited by 4 · see citing works
Profiling neurotransmitter-evoked glial responses by RNA-sequencing analysis
Wang, M., & Ho, M. (2023) · Frontiers in Neural Circuits · doi:10.3389/fncir.2023.1252759 · Cited by 3 · see citing works
Adenosine signaling in glia modulates metabolic state-dependent behavior in Drosophila
Backer, J. D., Karges, T., Papst, J., Pınar, Z. N., Coman, C., Ahrends, R., Xu, Y., García‐Cáceres, C., & Kadow, I. C. G. (2025) · Cell Reports · doi:10.1016/j.celrep.2025.115765 · Cited by 4 · see citing works
Osorio, N., Martineau, M., Fortea, M., Rouget, C., Pénalba, V., Lee, C. J., Boesmans, W., Rolli‐Derkinderen, M., Patel, A. V., Mondielli, G., et al. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.04.19.537136 · Cited by 3 · see citing works
Guttenplan, K. A., Maxwell, I., Santos, E. N., Borchardt, L. A., Manzo, E., Abalde-Atristain, L., Kim, R. D., & Freeman, M. R. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.09.23.614537 · Cited by 3 · see citing works
Sensory regulation of meal sorting in Aedes aegypti mosquitoes
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Du, C., Okuwa, S., Jia, L., Barreiro, M. R., Scott, S., Fonseca, J. E. S., Mabuchi, Y., Appadoo, S., Garcia, L., Rohrbach, S., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.05.30.657129 · Cited by 2 · see citing works
A High-Resolution Atlas of the Brain Predicts Lineage and Birth Order Underly Neuronal IdentityPreprint
Allen, A. M., Neville, M. C., Nojima, T., Alejevski, F., Agarwal, D., Sims, D., & Goodwin, S. F. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.06.04.657818 · Cited by 2 · see citing works
Self-citationVisceral signaling of post-ingestive malaise directs memory updating in DrosophilaPreprint
Senapati, B., Treiber, C. D., & Waddell, S. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.10.21.683769 · Cited by 2 · see citing works
Self-citationAdenosine signaling in glia modulates metabolic state-dependent behavior in DrosophilaPreprint
Backer, J. D., Karges, T., Papst, J., Coman, C., Ahrends, R., Xu, Y., García‐Cáceres, C., & Kadow, I. C. G. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.08.07.606811 · Cited by 1 · see citing works
Thirst increases astrocytic release and synthesis of D-serine to promote water procurement
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Self-citationSensory biology: Thirsty glia motivate water consumption
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Editorial: Neurobiology of Drosophila: the 19th NeuroFly-2022 meeting
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Transition in “Digital Brain” Researches, and Surrogate-based Generative Model
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Calcium dynamics in habenular astrocytes regulate active coping within behavioral transitions
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Dehydration, Formaldehyde, and Age-Related Cognitive Impairment
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Genetic sex of enteric neurons enables ovarian relaxin to gate maternal gut plasticityPreprint
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Glial mediation of hormonal actions on the Drosophila brain
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Intracellular amino acid scarcity sensing tunes protein hungerPreprint
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Self-citationA male-specific neural circuit for appetitive thirst in DrosophilaPreprint
Wang, B. P., Zhang, X., Shastry, S., Kaur, G., Fatima, N., & Wolf, F. W. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.10.08.757749
- 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
- ORCID
- Venue
- Current Biology
- Publisher
- Elsevier BV
- Published
- 2022-09
- Volume
- 32
- Issue
- 18
- Pages
- 3952-3970.e8
- ISSN
- 0960-9822 (ISSN-L)
- PMC
- PMC9616736
- 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
- hybrid
- doi.org
- Licence
- 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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