Fig. 9: Optogenetic stimulation of the VPChAT-BLA projection reduces pain thresholds and induces depression- and anxiety-like behaviours.

a–c Schematic diagram and representative images for unilateral optogenetic stimulation of the VP-BLA ChAT projection. d, e Mechanical PWT and thermal PWL on hind paws before, during, and after unilateral BLA light in ChR2 (n = 13) and eYFP (n = 13) mice. d PWT. ChR2: contralateral: F(1.555, 18.66) = 24.22, P < 0.001; t = 8.18, df = 12, P < 0.0001, off vs on; ipsilateral: F(1.983, 23.80) = 1.79, P = 0.19. eYFP: contralateral, F(1.993, 23.92) = 0.41, P = 0.67; ipsilateral, F(1.432, 17.18) = 3.19, P = 0.08, off vs on. e PWL. Contralateral: F(1.935, 23.22) = 128.1, P < 0.0001, t = 16.18, df = 12, P < 0.001, off vs on; ipsilateral: F(1.631, 19.57) = 0.17, P = 0.80. eYFP: contralateral, F(1.254, 15.04) = 1.81, P = 0.20; ipsilateral, F(1.831, 21.97) = 0.27, P = 0.27. f Schematic diagram for 3-day repetitive bilateral stimulation of the VPChAT-BLA projection. g, h Representative images (g) and summary (h) showing that repetitive photo-stimulation of the VPChAT-BLA projection increased the number of c-Fos-positive neurons in the BLA, measured 2 days after discontinuation of photo-stimulation. Left: t = 5.58, df = 22, P < 0.0001; Right: t = 3.81, df = 22, P = 0.001. no light: n = 12 sections from seven mice; light: n = 12 sections from six mice. i–l Behavioural tests in ChR2 (n = 12) and eGFP (n = 12) mice. i TST. T = 4.46, df = 22, P = 0.0002. j FST. t = 9.31, df = 22, P < 0.0001. k EPM. Time in open-arms: t = 3.92, df = 22, P = 0.0007. Open-arms entries: t = 3.05, df = 22, P = 0.006. l OFT. Immobility: F = 0.45, df = 22, P = 0.66. Time in center: t = 2.57, df = 22, P = 0.017. One-way repeated-measures ANOVAs with Bonferroni tests and Geisser–Greenhouse corrections were used for (d, e). Two-tailed t-tests were used for (h–l) (left panel). Kurskal Wallis one-way ANOVA on ranks test was used for l (right panel). *P < 0.05; **P < 0.01; ns not significant.