Fig. 6: Optogenetic manipulation of LHGABA-novelty ensemble modulates pain and anxiety-like behaviors. | Nature Communications

Fig. 6: Optogenetic manipulation of LHGABA-novelty ensemble modulates pain and anxiety-like behaviors.

From: Novelty exploration-activated ensemble in the lateral hypothalamus confers analgesic and anxiolytic effects

Fig. 6: Optogenetic manipulation of LHGABA-novelty ensemble modulates pain and anxiety-like behaviors.The alternative text for this image may have been generated using AI.

a Schematic diagram showing DOX-enabled, Cre-dependent expression of ChR2, Arch, or eYFP in LH GABAergic novelty ensemble of Vgat-Cre mice. Validation of ChR2 (b) and Arch (c) function. Representative expression, photocurrent traces, and peak current amplitudes (ChR2 n = 8, Arch n = 7 cells). Scale bar, 100μm. Blue light illumination (ChR2 n = 8, eYFP n = 8 mice): d Formalin-induced licking time (t = 2.29, P = 0.039) and bouts (t = 1.38, P = 0.19) during LH illumination (5 ms, 4 mW, 20 Hz). PWT and PWL 24 h post-CFA (e, PWT: F(1,14) = 15.52, P = 0.002; PWL: F(1,14) = 27.60, P = 0.0001) and 2 weeks post-SNI (f, PWT: F(1,14) = 14.84, P = 0.002; PWL: F(1,14) = 71.67, P < 0.0001). g CPP time in paired chamber (eYFP t = 0.56, P = 0.60; ChR2 t = 2.92, P = 0.027). OFT tracks (h), center time (i, t = 2.21, P = 0.046), distance (j, t = 1.73, P = 0.11), and velocity (k, t = 1.80, P = 0.095). EPM tracks, open arms time (t = 2.84, P = 0.014), and frequency (t = 2.29, P = 0.038). Yellow light illumination (Arch n = 8, eYFP n = 8 mice): n Formalin-induced licking time (t = 2.50, P = 0.026) and bouts (t = 0.22, P = 0.831) during LH illumination (589 nm, 3 mW). PWT and PWL post-CFA (o, PWT: F(1,14) = 12.53, P = 0.003; PWL: F(1,14) = 50.98, P < 0.0001) and post-SNI (p, PWT: F(1,14) = 7.23, P = 0.018; PWL: F(1,14) = 28.21, P = 0.0001). q CPA time in paired chamber (Arch t = 2.47, P = 0.048; eYFP t = 1.33, P = 0.22). OFT tracks (r), center time (s, t = 3.48, P = 0.008), distance (t, t = 0.79, P = 0.44), and velocity (u, t = 0.83, P = 0.42). v, w EPM tracks, open arms time (t = 3.41, P = 0.011), and frequency (t = 2.56, P = 0.02). *P < 0.05, **P < 0.01, n.s, not significant. Two-sided unpaired t-test (d, i-k, m, n, s-u, w), two-way ANOVA with Tukey’s post hoc test (e, f, o, p), two-sided paired t-test (g, q). Data are mean ± SEM. Blue/yellow dots in (g, q) represent light-paired sides; black dots indicate non-stimulated sides. Dashed squares in (h, r) outline OFT center zone. Black outlines in (l, v) denote EPM closed arms. Created in BioRender. Zhou, C. (2026) https://BioRender.com/ikcpymj. Source data are provided as a Source Data file.

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