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

Park, Annie; Croset, Vincent; Otto, Nils; Agarwal, Devika; Treiber, Christoph D.; Meschi, Eleanora; Sims, David; Waddell, Scott

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.

Citation

Park, A., Croset, V., Otto, N., Agarwal, D., Treiber, C. D., Meschi, E., Sims, D., & Waddell, S. (2022). Gliotransmission of D-serine promotes thirst-directed behaviors in Drosophila. Current Biology, 32(18), 3952-3970. https://doi.org/10.1016/j.cub.2022.07.038

• Journal Article Type: Article
• Acceptance Date: Jul 15, 2022
• Online Publication Date: Aug 12, 2022
• Publication Date: Sep 26, 2022
• Deposit Date: May 31, 2022
• Publicly Available Date: Sep 27, 2022
• Journal: Current Biology
• Print ISSN: 0960-9822
• Publisher: Cell Press
• Peer Reviewed: Peer Reviewed
• Volume: 32
• Issue: 18
• Pages: 3952-3970
• DOI: https://doi.org/10.1016/j.cub.2022.07.038
• Public URL: https://durham-repository.worktribe.com/output/1203274
• Related Public URLs: https://www.biorxiv.org/content/10.1101/2022.03.07.483255v1