Fig. 5: Bidirectional control of CCK neurons bidirectionally modulates depression-related behavior. | Nature Communications

Fig. 5: Bidirectional control of CCK neurons bidirectionally modulates depression-related behavior.

From: A cell-type-specific circuit of somatostatin neurons in the habenula encodes antidepressant action in male mice

Fig. 5

a–d Schematic diagram (a) and the expression of NpHR3 in CCK neurons (b, n = 10 mice) and their exon terminals (c, n = 10 mice) and single unit recordings of CCK neuronal inhibition from freely behaving mice (d) with fiber locations, error bar represents mean ± SEM in (d). e–g Optogenetic inhibition (yellow: light on) of CCK neurons generates antidepressant action, based on the sucrose-CPP (e), the TST (f), and the TBP assays (g). Data are presented as mean ± SEM (n = 10 mice per group, ON: CMSGFP vs. CMSNpHR3 **p = 2.92 × 10−4 in (e), ON: **p = 4.03 × 10−4 in (f), ON: ***p = 3.43 × 10−5 in (g), two-way repeated measures ANOVA, ns, no significant difference). Representative heatmaps in Fig. 5e show the CPP of CMS CCKNpHR3GFP mice before and during light illumination. In this study, depression-like behaviors in CCKGFP and CCKNpHR3GFP mice were induced by CMS, and the non-CMS CCKGFP and CCKNpHR3GFP mice were used as controls. h Plots showing the percentage of activated SST neurons following optogenetic inhibition of CCK neurons highly correlate with antidepressant action based on the CPP and the TBP assays. Pearson’s r (2-tailed). Data are presented as mean ± SEM (n = 10 mice per group, p = 4.2 × 10−3 for CPP, p = 1.28 × 10-4 for TBP). i–k Schematic diagram (i) and the expression of ChR2-GFP in CCK neurons (j, n = 10 mice), and single-unit recordings of CCK neuronal excitation from freely behaving mice (k) with fiber locations, error bar represents mean ± SEM in (k). l–n Optogenetic activation (blue: light on) of CCK neurons induces depression-related phenotypes, based on the assays in the TST (l), the sucrose-CPP (m), and the TBP (n). Data are presented as mean ± SEM (n = 10 mice per group, ON: GFP vs. ChR2 ***p = 3.83 × 10−5 in (l), ON: **p = 1.46 × 10-4 in (m), ON: ***p = 7.50 × 10−7 in (n), ns, no significant difference, two-way repeated measures ANOVA). CCK: cholecystokinin; UCP: unconditioned place (water); CP: conditioned place (12% sucrose). Source data are provided as a Source Data file.

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