Fig. 3: TMN-SUB histaminergic circuit bidirectionally regulates accelerated locomotion in alert condition.

a Schematic of injection of AAV-CAG-FLEX-oChIEF-tdTomato into the TMN of HDC-CreERT2 mice (top), and optic fiber position in SUB (bottom), scale bar = 100 µm. b Representative velocity curve and speed upon TMN-SUB circuit activation in open field test. n = 9 mice, **p = 0.0086. Representative traveled tracks (c), distance (d), representative velocity distribution (e), and 5-speed subsections analysis for active time (f), distance (g) of HDC-CreERT2: oChIEF mice, n = 10 mice (d: ***p = 0.0007; f: **p = 0.0036, *p = 0.0471, p = 0.1720, p = 0.1763, **p = 0.0030; g: **p = 0.0026, p = 0.3348, *p = 0.0296, *p = 0.0116, **p = 0.0040). h Schematic of injection of AAV-CAG-FLEX-ArchT-GFP into the TMN of HDC-CreERT2 mice (top), and optic fiber position in SUB (bottom), scale bar = 100 µm. i Representative velocity curve and speed upon TMN-SUB circuit inhibition in open field test. n = 9, p = 0.3502. Representative traveled tracks (j), distance (k), velocity distribution (l), and 5-speed subsections analysis for active time (m), distance (n) of HDC-CreERT2: ArchT mice, n = 11 mice (k: p = 0.5722; m: p = 0.1325, p = 0.4365, p = 0.1211, p = 0.0811, p = 0.8820; n: p = 0.8981, p = 0.6708, p = 0.2177, p = 0.4035, p = 0.6132). Effects of optogenetic activation of TMN-SUB terminals on distance (o), average speed heatmap (p), and max escape speed (q) of HDC-CreERT2: oChIEF mice during alert-escape test. n = 12 mice (o: **p = 0.0044; q: **p = 0.0063). Effects of optogenetic inhibition of TMN-SUB terminals on distance (r), average speed heatmap (s), and max escape speed (t) of HDC-CreERT2: ArchT mice during alert-escape test. n = 10 mice (r: *p = 0.0176; t: **p = 0.0073). Two-tailed Student’s t test for (b, d, f, g, i, k, m–o, q, r, t). Schematics in a, h were drew by PowerPoint. Bar graphs represent mean ± SEM. Source data are provided as a Source Data file.