Fig. 7: Optogenetic manipulation of LH glutamatergic novelty ensemble modulates pain and anxiety-like behavior. | Nature Communications

Fig. 7: Optogenetic manipulation of LH glutamatergic novelty ensemble modulates pain and anxiety-like behavior.

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

Fig. 7: Optogenetic manipulation of LH glutamatergic novelty ensemble modulates pain and anxiety-like behavior.The alternative text for this image may have been generated using AI.

a Viral strategy for DOX-enabled, Cre-dependent expression of ChR2, Arch, or eYFP in the LH glutamatergic novelty ensemble of Vglut2-Cre mice. Validation of ChR2 (b) and Arch (c) showing viral expression, photocurrents, and peak amplitudes (n = 7 cells/group). Scale bar, 100 μm. LH blue light illumination (ChR2). d Formalin-induced licking time (t = 2.71, P = 0.018) and bouts (t = 3.07, P = 0.009). PWT and PWL in CFA (e, PWT: F(1, 13) = 27.11, P = 0.0002; PWL: F(1, 13) = 23.95, P = 0.0003) and SNI (f, PWT: F(1, 13) = 120.6, P < 0.0001; PWL: F(1, 13) = 36.11, P < 0.0001) mice. g Chamber time for eYFP (t = 1.39, P = 0.21, n = 8 mice) and ChR2 (t = 3.00, P = 0.024, n = 7 mice). OFT tracks (h), center time (i, t = 3.27, P = 0.006), distance (j, t = 2.10, P = 0.006) and velocity (k, t = 2.1, P = 0.064). l EPM open arm time (t = 2.19, P = 0.047) and frequency (t = 2.71, P = 0.01). ChR2 n = 7, eYFP n = 8 mice/group for (d–f, h-l). LH yellow light illumination (Arch). m Formalin-induced licking time (t = 2.29, P = 0.039) and bouts (t = 0.75, P = 0.47). PWT and PWL in CFA (n, PWT: F(1, 13) = 7.40, P = 0.02; PWL: F(1, 13) = 4.93, P = 0.045) and SNI (o, PWT: F(1, 13) = 10.82, P = 0.006; PWL: F(1, 13) = 9.15, P = 0.009). p CPP chamber time for Arch (t = 2.79, P = 0.03, n = 7 mice) and eYFP (t = 0.92, P = 0.39, n = 8 mice). OFT tracks (q), center time (r, t = 3.58, P = 0.006), distance (s, t = 0.56, P = 0.58) and velocity (t, t = 0.59, P = 0.56). u EPM open arm time (t = 2.18, P = 0.047) and frequency (t = 5.19, P = 0.0009). Arch n = 7 (m-o, q-t) or 8 (u), eYFP n = 8 mice/group. *P < 0.05, **P < 0.01. Two-way RM ANOVA with Tukey’s post hoc test (e, f, n, o), two-sided paired t-test (g, p), and two-sided unpaired t-test (d, i-m, r–u). Dots in (g, p) mark light-paired (color) and non-stimulated (black) sides. Dashed squares in (h, q) outline OFT center zone. Black outlines in (l, u) denote EPM closed arms. Data are mean ± SEM. Created in BioRender. Zhou, C. (2026) https://BioRender.com/ikcpymj. Source data are provided as a Source Data file.

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