Fig. 6: H2R in SUB glutamatergic neurons mainly mediate the pro-locomotion function of histamine-tuned circuit.

a WT mice were implanted cannula in SUB, scale bar = 400 µm. Effects of administration of H3R antagonist on distance (b), speed (c) and 5-speed subsections analysis for active time (d), distance (e) in open field test. n = 9 mice (****p < 0.0001 for (b) and (c); d: *p = 0.0154, *p = 0.0195, **p = 0.0073, p = 0.6811, ***p = 0.0003; e: p = 0.9120, p = 0.3507, p = 0.0719, p = 0.0535, ****p < 0.0001). Effects of Thio and H1R/H2R-agonist on distance (f), speed (g) in open field test, n = 13, 13, 13, 14 mice for PBS, Thio, 2-Pel, Amt group (f: *p = 0.0148, **p = 0.0028, *p = 0. 0193; g: *p = 0.0141, **p = 0.0029, *p = 0. 0201). Effects of Thio combined with H1R/H2R-related drugs on distance (h), speed (i), n = 8, 9, 9, 9, 8, 10, 9 mice for PBS, Thio, Pyr + Thio, U73122 + Thio, Zol + Thio, ZD7288 + Thio, SQ22536 + Thio group (h: **p = 0.0035 vs. PBS; ^##p = 0.0049, ^####p < 0.0001, ^##p = 0.0019 vs. Thio; i: *p = 0.0120 vs. PBS; ^#p = 0.0172, ^####p < 0.0001, ^##p = 0.0067 vs. Thio), ns with respect to Thio group. j CaMKIIα-Cre were injected with knockdown virus (j1), validation of H1R/H2R expression with CaMKIIα immunostaining, scale bar = 10 µm (j2). Distance (k), and speed (l) in open field test of H1R/H2R knockdown mice, n = 9, 9 for AAV-GFP group; n = 9, 10 for AAV-shHrh1 group; n = 12, 12 for AAV-shHrh2 group (k: ***p = 0.0004 vs. PBS, ^&&p = 0.0017 vs. AAV-GFP + Thio; l: ***p = 0.0005 vs. PBS, ^&&p = 0.0017 vs. AAV-GFP + Thio). Two-tailed Student’s t test for (b–e, k, l) and one-way ANOVA followed by post-Dunnett’s test for (f–i). Schematics in a, j1 were drew by PowerPoint. Bar graphs represent mean ± SEM. Source data are provided as a Source Data file.