Drosulfakinin signaling encodes early-life memory for adaptive social plasticity
- Department of Biological Sciences, Ulsan National Institute of Science and Technology, Republic of Korea
- Department of Biomedical Engineering, Ulsan National Institute of Science and Technology, Republic of Korea
- Research Center for Cellular Identity, Korea Advanced Institute of Science and Technology, Republic of Korea
- Center for Genomic Integrity, Institute for Basic Science, Republic of Korea
- Graduate School of Health Science and Technology, Ulsan National Institute of Science and Technology, Republic of Korea
- Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Republic of Korea
- Graduate School of Stem Cell and Regenerative Biology, Korea Advanced Institute of Science and Technology, Republic of Korea
Figures
Figure 1
Social network behavior (SNB) is a quantitative trait in a natural Drosophila population.
(A) The 10 min video recording of SNB in a group of 16 male flies. Representative snapshot images at each quarter time point (Q1, Q2, Q3, and Q4) were obtained from Drosophila strains with high (top, short social distance [SD]) or low clustering properties (bottom, long SD). (B) The definition of SD. SD was measured in each fly over the 10 min recording and averaged from a given group. Representative SD dynamics from short- (top) or long-SD strains (bottom) were shown. Dotted lines, group-averaged SD over the 10 min recordings. (C) Quantitative assessment of SNB by ranking SD, walking speed, and centroid velocity among 175 DGRP lines. Data represent means ± SEM (n = 5). (D) Significant correlation among SD, walking speed, and centroid velocity. ***p<0.001, as determined by Spearman correlation analysis. Red, representative short-SD lines; blue, representative long-SD lines.
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Figure 1—source data 1
Correlation of SD, walking speed, and centroid velocity across 175 DGRP lines.
- https://cdn.elifesciences.org/articles/103973/elife-103973-fig1-data1-v2.xlsx
Figure 2 with 4 supplements
Short- and long-social distance (SD) lines exhibit distinct social network behavior (SNB).
(A, B) SNB dynamics in short-SD (A) and long-SD lines (B). SD dynamics in a representative group of 16 male flies over the 10 min recordings (left, n = 16), quarter-averaged SD (middle, n = 8), and quarter-averaged walking speed (right, n = 8) were shown for each Drosophila Genetics Reference Panel (DGRP) line. Error bars indicate SEM. n.s., not significant; *p<0.05, **p<0.01, ***p<0.001 as determined by paired t-test (DGRP73, DGRP563, DGRP370, DGRP707, and DGRP317 for quarter-averaged SD; DGRP563, DGRP360, and DGRP317 for quarter-averaged walking speed) or Wilcoxon matched-pairs signed rank test (DGRP360 for quarter-averaged SD; DGRP73, DGRP370, and DGRP707 for quarter-averaged walking speed). (C) The 10 min locomotion trajectories of representative individual flies from short- (red) or long-SD lines (blue). (D) Cumulative travel distances of individual flies over the 10 min recording. Colored lines represent means (n = 128).
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Figure 2—source data 1
Quantitative locomotor metrics in short- and long-SD DGRP lines.
- https://cdn.elifesciences.org/articles/103973/elife-103973-fig2-data1-v2.xlsx
Figure 2—figure supplement 1
Social network behaviors in the three representative Drosophila Genetics Reference Panel (DGRP) lines displaying short or long social distance (SD).
(A) Centroid trajectories of short- (red; DGRP73, 563, 370) or long-SD lines (blue; DGRP360, 707, 317) over the 10 min video recording. (B) The short-SD lines exhibit slow walking speeds and low centroid velocities compared to the long-SD lines. Social isolation significantly impaired SNB only in the short-SD lines. Data represent means ± SEM (n = 8). n.s., not significant; *p<0.05, **p<0.01, ***p<0.001, as determined by unpaired t-test. (C) Long-SD individuals show longer travel distances than short-SD ones during the 10 min video recording. Data represent means ± SEM (n = 8 for averaged data; n = 128 for individual data). ***p<0.001 as determined by ordinary one-way ANOVA with Tukey’s multiple comparisons test (averaged data) or aligned ranks transformation ANOVA with Wilcoxon rank-sum test (individual data).
Figure 2—figure supplement 2
Neither short- nor long-social distance (SD) lines reduce their walking speeds over time when individual flies from group cultures are isolated.
A single male fly from each Drosophila Genetics Reference Panel (DGRP) line was placed in the arena for social network behaviors (SNB) analysis and video-recorded for 10 min to quantify its locomotor activity. Data represent means ± SEM (n = 20). n.s., not significant; *p<0.05, **p<0.01, as determined by Wilcoxon matched-pairs signed rank test (DGRP73, DGRP563, DGRP370, and DGRP360) or paired t-test (DGRP707 and DGRP317).
Figure 2—figure supplement 3
The clustering property of each Drosophila Genetics Reference Panel (DGRP) line persists in a large arena.
A group of 16 male flies was placed in a large arena (8.5 cm in diameter), and their locomotor behaviors were video-recorded for 10 min. Representative snapshot images were obtained at each quarter of the 10 min recording. The heatmap illustrates the relative distribution of individual flies in the arena.
Figure 2—figure supplement 4
Neither short- or long-social distance (SD) lines display male–male courtship behavior.
(A) A representative snapshot image of courtship chaining behavior (dotted circle) in a group of rut1 mutant flies. (B) The chaining index was calculated from the 10 min video-recording of 16 male flies in the arena. Data represent means ± SEM (n = 8). Drosophila Genetics Reference Panel (DGRP) lines did not display any detectable courtship chaining behavior.
Figure 3
Early-life social experience confers beneficial effects on Drosophila development.
(A) Larval clustering in short- (red) or long-social distance (SD) lines (blue). % clusters were calculated from 30 vials. Arrows indicate individual larvae. Scale bar = 0.5 mm. (B) Schematic for grouped (grp) vs. developmentally isolated (iso) culture conditions. (C, D) Grouped culture compensated for low food accessibility in the short-SD larvae. Aligned ranks transformation ANOVA detected significant effects of SD trait and social isolation on both digging depth (C, p<0.0001) and food intake (D, p<0.0001), and their significant interaction effects were detected only on digging depth (C, p=0.0338). Data represent means ± SEM (n = 36; 12 per line × 3 lines). ***p<0.001, as determined by Wilcoxon rank sum test. (E–G) Grouped culture rescued developmental delay and low male-progeny ratio in the short-SD larvae. Aligned ranks transformation ANOVA or ordinary two-way ANOVA detected significant effects of SD trait and social isolation on developmental time (E, p<0.0001), eclosion success (F, p=0.0116 for SD trait; p<0.0001 for social isolation), and male progeny ratio (G, p<0.0001). Significant interaction effects between SD trait and social isolation were also detected on developmental time (E, p<0.0001) and male progeny ratio (G, p<0.0001). Data represent means ± SEM (n = 24; 8 per line × 3 lines). n.s., not significant; *p<0.05, ***p<0.001, as determined by Wilcoxon rank sum test (developmental time and male progeny ratio) or Tukey’s multiple comparisons test (eclosion success).
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Figure 3—source data 1
Quantitative analysis of larval SNB and developmental metrics.
- https://cdn.elifesciences.org/articles/103973/elife-103973-fig3-data1-v2.xlsx
Figure 4 with 5 supplements
Early-life social experience confers beneficial effects on social foraging in adult Drosophila.
(A) Experimental scheme for assessing social interactions in a maze assay. Representative images were shown for a group of Drosophila strains with high (short latency) or low social foraging (long latency). (B) Pioneer groups of flies from either grouped (grp) or isolated cultures (iso) were effectively trained in the maze assay, but social isolation of both short- (red, DGRP73) and long-SD flies (blue, DGRP360) blunted the pioneer effects on food-seeking behaviors in a group of naive flies. Two-way repeated measures ANOVA detected significant effects of training (p<0.0001 for DGRP73 and DGRP360) but not social isolation on latency during the training session of pioneer groups. Ordinary two-way ANOVA also detected significant interaction effects of pioneer and social isolation on latency during the maze test (p=0.0131 for DGRP73; p=0.0310 for DGRP360). Data represent means ± SEM (n = 6‒16). n.s., not significant; *p<0.05, **p<0.01, ***p<0.001, as determined by Sidak’s multiple comparisons test (training session) or Tukey’s multiple comparisons test (maze test). (C) Experimental scheme for assessing injury-induced social network behavior (SNB) plasticity. GTI, grouped-to-isolated culture transition; ITG, isolated-to-grouped culture transition. (D) Physical injury induced clustering behaviors in group-cultured but not developmentally isolated flies. Data represent means ± SEM (n = 8). n.s., not significant; *p<0.05, **p<0.01, ***p<0.001, as determined by one-way ANOVA with Tukey’s multiple comparisons test.
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Figure 4—source data 1
Quantitative analysis of adult SNB and social plasticity.
- https://cdn.elifesciences.org/articles/103973/elife-103973-fig4-data1-v2.xlsx
Figure 4—figure supplement 1
Social isolation blunts pioneer effects on food-seeking behaviors in a group of naive flies.
Pioneer groups of short- (DGRP563 and DGRP370) and long-social distance (SD) lines (DGRP707 and DGRP317) were effectively trained in the maze assay but they failed to improve the efficiency of food-seeking behaviors with groups of socially isolated flies. Data represent means ± SEM (n = 6–12). n.s., not significant; *p<0.05, **p<0.01, ***p<0.001, as determined by two-way repeated measures ANOVA with Sidak’s multiple comparisons test (pioneer training) or two-way ANOVA with Tukey’s multiple comparisons test (group test). Grp, grouped; iso, isolated.
Figure 4—figure supplement 2
Rutabaga-dependent working memory is dispensable for social memory.
(A) Plasticity mutants of rutabaga (rut1 and rut2080) fail to improve food-seeking behaviors in the maze after repetitive trainings. Canton-S (CS) served as a wild-type control. Data represent means ± SEM (n = 9 for rut1; n = 8 for rut2080). n.s., not significant; **p<0.01, ***p<0.001, as determined by paired t-test. (B) rut mutants display injury-induced clustering comparable to control flies. Social distance (SD) was measured in group-cultured male flies under distinct experimental conditions (ctrl, control; inj, injured). Two-way ANOVA detected no significant interaction effects of genotype and inj on SD. Data represent means ± SEM (n = 8 for rut1; n = 10 for rut2080). *p<0.05, **p<0.01, as determined by Tukey’s multiple comparisons test.
Figure 4—figure supplement 3
Early-life social experience is necessary for social behavior plasticity in male flies.
(A) Physical injury induced clustering behaviors in group-cultured but not developmentally isolated flies. Social distance (SD) was measured in a group of male flies under distinct experimental conditions (ctrl, control; inj, injured; rec, recovered; grp, grouped; iso, isolated; GTI, grouped-to-isolated culture transition; ITG, isolated-to-grouped culture transition). Data represent means ± SEM (n = 8). n.s., not significant; *p<0.05, **p<0.01, ***p<0.001, as determined by one-way ANOVA with Tukey’s multiple comparisons test. (B) Female flies did not display injury-induced clustering. SD was measured in group-cultured female flies from individual Drosophila Genetics Reference Panel (DGRP) lines. Data represent means ± SEM (n = 8). n.s., not significant as determined by one-way ANOVA with Tukey’s multiple comparisons test.
Figure 4—figure supplement 4
Mechanical injury reduces walking speed and centroid velocity only in group-cultured long-social distance (SD) flies.
Locomotor activities were quantified in a group of long- and short-SD male flies under distinct experimental conditions (ctrl, control; inj, injured; rec, recovered; grp, grouped; iso, isolated). Two-way ANOVA detected significant interaction effects of inj and iso on walking speed and centroid velocity only in long-SD lines (***p<0.001 for DGRP360 and DGRP707; *p<0.05 for DGRP317, except centroid velocity). Data represent means ± SEM (n = 8). n.s., not significant; *p<0.05, **p<0.01, ***p<0.001, as determined by Tukey’s multiple comparisons test.
Figure 4—figure supplement 5
Loss of norpA function blocks injury-induced clustering in group-cultured male flies.
Social distance (SD) was measured in a group of male mutants for each sensory-pathway gene as described in Figure 1. Data represent means ± SEM (n = 8). n.s., not significant; *p<0.05, **p<0.01, ***p<0.001, as determined by two-way ANOVA with Tukey’s multiple comparisons test. Ctrl, control; inj, injured.
Figure 5 with 2 supplements
Social experience shapes gene expression profiles in Drosophila heads.
(A) Heatmaps for differentially expressed genes (DEGs, more than twofold difference with adjusted p<0.05) in short- vs. long-social distance (SD) lines (left); in grouped (grp) vs. isolated (iso) condition (right). Fly heads were harvested from individual Drosophila Genetics Reference Panel (DGRP) lines in grouped or isolated cultures and their gene expression profiles were analyzed by RNA sequencing. Averaged counts per million were converted to z-score for visualization. (B) Volcano plots for differentially expressed genes (DEGs) in short- vs. long-SD lines (top); in grp vs. iso flies (bottom). Social interactions evidently upregulated the neuropeptide Drosulfakinin (Dsk) expression. (C) Overlapping DEGs in grp vs. iso conditions across DGRP lines. Dsk was identified as a commonly upregulated gene by social interactions in short- (top, red) and long-SD lines (middle, blue). (D) Gene Ontology analysis reveals upregulation of select metabolic pathways upon social isolation. False discovery rate (FDR) < 0.05, as determined by Fisher’s exact test (grp vs. iso). (E) Significant phenotypic correlation of SNB to food intake, starvation-induced activity, and mean aggressive encounters among DGRP lines. Raw data for food intake (n = 52 DGRP lines), starvation-induced activity (n = 60 DGRP lines), and aggression (n = 57 DGRP lines) were obtained from previous studies (Garlapow et al., 2015; Shorter et al., 2015; Chi et al., 2021) and then aligned to SD, centroid velocity, and walking speed in the corresponding DGRP lines that were measured by our SNB analyses. *p<0.05, **p<0.01, ***p<0.001, as determined by Spearman correlation analysis. (F) Expression heatmap for genes implicated in feeding, adult locomotor behavior, and aggression. Downregulation of Dsk and its two receptors (CCKLR-17D1 and CCKLR-17D3) by social isolation was visualized in relevant gene categories.
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Figure 5—source data 1
Normalized gene expression in individual DGRP lines under grouped vs. isolated culture conditions.
- https://cdn.elifesciences.org/articles/103973/elife-103973-fig5-data1-v2.xlsx
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Figure 5—source data 2
DEG analyses between distinct social groups (short vs. long SD; or grouped vs. isolated).
- https://cdn.elifesciences.org/articles/103973/elife-103973-fig5-data2-v2.xlsx
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Figure 5—source data 3
Comparative analyses of social group-specific DEGs from independent studies.
- https://cdn.elifesciences.org/articles/103973/elife-103973-fig5-data3-v2.xlsx
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Figure 5—source data 4
DEG analyses among individual DGRP lines.
- https://cdn.elifesciences.org/articles/103973/elife-103973-fig5-data4-v2.xlsx
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Figure 5—source data 5
Correlation of SNB to food intake, starvation-induced activity, and aggression among DGRP lines.
- https://cdn.elifesciences.org/articles/103973/elife-103973-fig5-data5-v2.xlsx
Figure 5—figure supplement 1
Cross-study analyses of social context-dependent differentially expressed genes (DEGs) highlight Dsk as the most prominently upregulated gene under socially enriched conditions.
(A) Venn diagrams depict the numbers of upregulated genes under grouped (top, grp) and socially isolated conditions (bottom, iso), as identified by the previous and current studies. The numbers of overlapping DEGs between independent gene expression analyses were shown accordingly. (B) Venn diagrams illustrate the overlap of DEGs between short-social distance (SD) lines and group-culturing conditions (top, short SD vs. grp) and between long-SD lines and socially isolated conditions (bottom, long SD vs. iso).
Figure 5—figure supplement 2
Long-social distance (SD) flies display higher aggression than short-SD flies.
A pair of male flies from each Drosophila Genetics Reference Panel (DGRP) line were starved for 6 hr and then placed into a circular arena with yeast paste and a female carcass in the center. The number of lunges was counted during the 10 min video recording. Data represent means ± SEM (n = 6). *p<0.05, as determined by one-way ANOVA with Tukey’s multiple comparisons test.
Figure 6 with 2 supplements
Drosulfakinin (Dsk) neuron activity encodes social experience.
(A, B) Social experience elevates DSK levels in the Drosophila brains. Whole-mount brains from each Drosophila Genetics Reference Panel (DGRP) line in grouped (grp) or socially isolated cultures (iso) were co-immunostained with anti-DSK (green) and anti-BRUCHPILOT antibodies (BRP, a synaptic protein; magenta). The fluorescent DSK signals from confocal images were quantified using ImageJ. Ordinary two-way ANOVA or aligned ranks transformation ANOVA detected significant effects of social isolation on DSK levels in MP1a/MP1b/MP3 cell bodies and their projections (p<0.0001). The social distance (SD) trait effects (i.e., short vs. long SD) were more evident on DSK levels in cell bodies (p<0.0001). Data represent means ± SEM (n = 13). n.s., not significant; **p<0.01, ***p<0.001, as determined by Tukey’s multiple comparisons test (MP1a/MP1b cell bodies and MP1a projections) or Wilcoxon rank sum test (MP3 cell bodies and projections). Scale bar = 40 µm. (C) Social experience and physical injury elevate DSK neuron activity. Social isolation masked an injury-induced Ca2+ increase in the MP1a neurons among other DSK neurons as assessed by the genetically encoded Ca2+ sensor GCaMP in live-brain imaging. Two-way ANOVA detected significant effects of social isolation (p<0.0001) and injury (inj, p<0.01) on GCaMP levels in DSK neurons. Data represent means ± SEM (n = 10). n.s., not significant; *p<0.05, **p<0.01, ***p<0.001, as determined by Tukey’s multiple comparisons test. Scale bar = 5 µm. (D–F) Social experience strengthens postsynaptic signaling of DSK neurons only in males. Whole-mount brains were dissected from group-cultured (grp) or isolated (iso) flies and immunostained with anti-DSK antibody (white). Postsynaptic partner of DSK neurons was visualized by the heterologous ligand-receptor signaling embedded in the transsynaptic mapping transgene (Dsk>trans-Tango, magenta) while DSK neurons were further labeled by the presynaptic marker of the trans-Tango (green). The fluorescent trans-Tango signals and anti-DSK staining intensities from confocal images were quantified using ImageJ. Aligned ranks transformation ANOVA or ordinary 2-way ANOVA detected significant interaction effects of social isolation and gender on trans-Tango signals (E, p<0.0001) and DSK levels in MP1a projection (F, p<0.0001). Data represent means ± SEM (n = 13). n.s., not significant; ***p<0.001, as determined by Wilcoxon rank sum test (trans-Tango signals) or Tukey’s multiple comparisons test (DSK levels). Scale bar = 40 µm.
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Figure 6—source data 1
Quantitative analysis of DSK neuron activities under distinct social contexts.
- https://cdn.elifesciences.org/articles/103973/elife-103973-fig6-data1-v2.xlsx
Figure 6—figure supplement 1
Neither social experience nor physical injury affects transgenic DenMark expression in DSK neurons.
(A) Transgenic Dsk-Gal4 flies (Dsk>GCaMP7f and Dsk>DenMark + SytGFP) and heterozygous controls (Dsk-Gal4/+) display social experience-dependent plasticity of social network behavior (SNB). Social distance (SD) was measured in a group of transgenic male flies under distinct experimental conditions (ctrl, control; inj, injured; grp, grouped; iso, isolated). Data represent means ± SEM (n = 8). n.s., not significant; ***p<0.001, as determined by two-way ANOVA with Tukey’s multiple comparisons test. (B) Dendrites (DenMark, magenta) and axons (SytGFP, green) in DSK neurons were visualized by confocal imaging of a whole-mount transgenic brain (Dsk>DenMark + SytGFP). Scale bar = 40 µm. (C) Social isolation or mechanical injury did not affect the transgenic DenMark expression in DSK neurons. The fluorescence intensities of the DenMark signals in DSK neurons were quantified from confocal images using ImageJ. Data represent means ± SEM (n = 6). n.s., not significant as determined by two-way ANOVA with Tukey’s multiple comparisons test. Dotted lines indicate ROI. Scale bar = 5 µm.
Figure 6—figure supplement 2
Neither social experience nor physical injury affects circadian-clock neuron activity.
(A) Circadian-clock neurons expressing the neuropeptide pigment-dispersing factor were visualized in whole-mount adult brain by the combination of Pdf-Gal4 driver and red fluorescent protein transgenes (Pdf>mRFP). Arrows in each hemisphere indicate PDF-expressing large ventral lateral neurons (l-LNv). Scale bar = 40 µm. (B) The genetically encoded Ca2+ sensor GCaMP was expressed by the Pdf-Gal4 driver (Pdf>GCaMP7f) and the transgenic flies were harvested under distinct experimental conditions (ctrl, control; inj, injured; grp, grouped; iso, isolated). Live-brain Ca2+ imaging was then conducted in dissected brains. The GCaMP signals in l-LNv were quantified using ImageJ. Data represent means ± SEM (n = 5). n.s., not significant as determined by two-way ANOVA with Tukey’s multiple comparisons test. Scale bar = 5 µm.
Figure 7 with 3 supplements
Genetic manipulations of Drosulfakinin (DSK) signaling imitate social experience.
(A) DskattP mutant brain expresses barely detectable DSK peptides. Whole-mount brains from Canton S (CS, a wild-type control) and DskattP mutant flies were co-immunostained with anti-DSK (green) and anti-BRUCHPILOT antibodies (BRP, a synaptic protein; magenta). Scale bar = 40 µm. (B, C) Genetic silencing of DSK-CCKLR-17D1 signaling by genomic deletions (DskattP or CCKLR-17D1attP) or DSK depletion (Dsk >DskRNAi) blocks injury-induced clustering behaviors. Data represent means ± SEM (n = 8). n.s., not significant; **p<0.01, ***p<0.001, as determined by two-way ANOVA with Tukey’s multiple comparisons test. (D, E) Conditional blockade of DSK neuron transmission at larval stage is sufficient to blunt social experience-dependent plasticity of social network behavior (SNB). Transgenic crosses for DSK-specific expression of the temperature-sensitive shibire allele (Dsk >shits) were kept at either restrictive (29°C) or permissive temperature (18°C) for synaptic transmission until the end of larval stage. Two-way ANOVA detected significant interaction effects of injury (inj) and temperature on social distance (SD) in Dsk>shits flies (p=0.0169) but not in heterozygous controls (p=0.7549 for Dsk-Gal4/+; p=0.2030 for shits/+). Data represent means ± SEM (n = 6). n.s., not significant; *p<0.05, **p<0.01, ***p<0.001, as determined by Tukey’s multiple comparisons test. (F) CCKLR-17D1 neurons display sexually dimorphic dendrites around MP1 projections. Transgenic male or female brains (CCKLR-17D1>DenMark + SytGFP) were immunostained with anti-DSK antibody to visualize DSK neuron projections (white) along with dendrites (DenMark, magenta) and axons (SytGFP, green) of neurons expressing CCKLR-17D1-Gal4 knock-in. Scale bar = 40 µm. (G) Transgenic excitation of CCKLR-17D1 neurons confers injury-induced plasticity of SNB in socially isolated males but not females. Two-way ANOVA detected significant interaction effects of injury (inj) and social isolation on SD in male heterozygous controls (p=0.0040 for 17D1-Gal4/+; p=0.0007 for NaChBac/+) but not in all the other genotypes. Data represent means ± SEM (n = 8). n.s., not significant; *p<0.05, **p<0.01, as determined by Tukey’s multiple comparisons test.
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Figure 7—source data 1
Quantitative analysis of SNB plasticity in genetic and transgenic Drosophila models for DSK-DSK receptor signaling.
- https://cdn.elifesciences.org/articles/103973/elife-103973-fig7-data1-v2.xlsx
Figure 7—figure supplement 1
Transgenic Dsk RNAi effectively depletes DSK peptides in the adult brain.
The Dsk RNAi transgene was expressed in DSK neurons by the Dsk-Gal4 knock-in driver (Dsk>DskRNAi). Whole-mount transgenic brains were co-immunostained with anti-DSK (green) and anti-BRP (magenta) antibodies. Heterozygous flies for Gal4 (Dsk-Gal4/+) or RNAi transgenes (DskRNAi/+) served as negative controls. Scale bar = 40 µm.
Figure 7—figure supplement 2
Genomic deletions of CCKLR-17D1 but not CCKLR-17D3 suppress injury-induced clustering in group-cultured male flies.
Deletion mutants of the two Dsk receptor genes (CCKLR-17D1 and CCKLR-17D3) and hemizygous control flies (+/Y) were obtained from standard group cultures. Social distance (SD) was measured in a group of male flies as described in Figure 1. Two-way ANOVA detected significant interaction effects of injury (inj) with CCKLR-17D1 deletions (p=0.0404 for CCKLR-17D1Δ1; p=0.0254 for CCKLR-17D1Δ2) but not with CCKLR-17D3 deletions (p=0.1051 for CCKLR-17D3Δ1; p=0.6697 for CCKLR-17D3Δ2) on SD. Data represent means ± SEM (n = 8). n.s., not significant; *p<0.05, **p<0.01, ***p<0.001, as determined by Tukey’s multiple comparisons test.
Figure 7—figure supplement 3
Transgenic silencing of CCKLR-17D1 neurons suppresses injury-induced clustering in group-cultured male flies.
Synaptic transmission in CCKLR-17D1 neurons was blocked by transgenic expression of a tetanus toxin light chain (17D1>TNT). Heterozygous flies for Gal4 (17D1-Gal4/+) or TNT transgenes (TNT/+) served as negative controls. Two-way ANOVA detected significant interaction effects of genotype and injury (inj) on SD (p=0.0003 for 17D1-Gal4/+vs. 17D1>TNT; p=0.0012 for TNT/+vs. 17D1>TNT). Data represent means ± SEM (n = 8). n.s., not significant; ***p<0.001, as determined by Tukey’s multiple comparisons test.
Figure 8
A working model for early-life social memory and the experience-dependent plasticity of social network behavior (SNB).
Social distancing is an inheritable trait in Drosophila. Diverse genetic pathways contribute to active social preferences while the clustering property may have evolved to compensate for inferior traits in individuals and confer their group fitness. Nonetheless, Drosophila can tune their social distance depending on physiological states (e.g., mechanical injury) and this feature of SNB is defined as ‘social plasticity’. In fact, the social plasticity requires early-life social experience or ‘social memory’ during development. Group culturing elevates DSK expression and DSK neuron activity to reinforce its postsynaptic signals likely to the cognate receptor CCKLR-17D1. The activation of DSK-CCKLR-17D1 pathway thus encodes early-life social experience in developing brains to support social plasticity in adults.
Author response image 1
The circular arena for SNB recording.
Videos
Video 1
Social network behavior (SNB) in DGRP73 (grp+ctrl).
Video 2
Social network behavior (SNB) in DGRP360 (grp+ctrl).
Video 3
Social network behavior (SNB) in DGRP73 (large arena).
Video 4
Social network behavior (SNB) in DGRP360 (large arena).
Video 5
Social network behavior (SNB) in DGRP73 (grp+inj).
Video 6
Social network behavior (SNB) in DGRP360 (grp+inj).
Video 7
Social network behavior (SNB) in DGRP73 (iso+ctrl).
Video 8
Social network behavior (SNB) in DGRP360 (iso+ctrl).
Video 9
Social network behavior (SNB) in DGRP73 (iso+inj).
Video 10
Social network behavior (SNB) in DGRP360 (iso+inj).
Video 11
Aggression behaviors in DGRP73.
Video 12
Aggression behaviors in DGRP360.
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Drosulfakinin signaling encodes early-life memory for adaptive social plasticity
eLife 13:e103973.
https://doi.org/10.7554/eLife.103973
