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. 2022 Sep 26;32(18):3952–3970.e8. doi: 10.1016/j.cub.2022.07.038

Figure 4.

Figure 4

D-serine modulates water consumption via NMDARs

(A) Model of tripartite glutamatergic synapse showing aay-dependent synthesis of D-serine in astrocytes.

(B) Protocol for D-serine feeding and RNAi induction with water consumption experiments.

(C–G) Light blue section of lines indicate time on D- or L-serine food. Orange section of lines indicate period of water restriction.

(C) D- but not L-serine feeding increases water consumption (n = 20–23). ∗∗p < 0.01, Kruskal-Wallis ANOVA with Dunn’s multiple comparisons test.

(D) D-serine feeding rescues the water consumption defect in flies with aay knockdown (n = 15–18). p < 0.05, ∗∗p < 0.01, ordinary one-way ANOVA with Dunnett’s multiple comparisons test.

(E) Glial overexpression of D-amino acid oxidase (DAAO) reduces water consumption (n = 16–20). p < 0.05, ∗∗p < 0.01, ordinary one-way ANOVA with Dunnett’s multiple comparisons test.

(F) Flies harboring the F654A single site mutation in NMDAR1 exhibit increased water consumption. This mutation increases affinity for glycine/D-serine (n = 29–34). p < 0.05, Kruskal-Wallis ANOVA with Dunn’s multiple comparisons test.

(G) Flies harboring the K558Q amino acid substitution in NMDAR1 are insensitive to the D-serine induced increase in water consumption (n = 18–25). ∗∗p < 0.01, two-tailed Mann-Whitney test. Individual data points are single flies. Data are mean ± SEM.

See also Figure S4.