Fig. 2: Glutamate is essential for the analgesic and anti-anhedonia effects conferred by VGluT3DRN→VTA neural excitation. | Nature Communications

Fig. 2: Glutamate is essential for the analgesic and anti-anhedonia effects conferred by VGluT3DRN→VTA neural excitation.

From: A glutamatergic DRN–VTA pathway modulates neuropathic pain and comorbid anhedonia-like behavior in mice

Fig. 2

a, g Schematic of the experimental design. b Schematic diagram of viral injection and optical fiber implantation (left). Representative images (middle) and summary data (right) for the percentage of mCherry-expressing neurons co-localized with VGluT3 immunofluorescence, n = 9 sections from 3 mice. Scale bar, 50 μm. c, d Mechanical paw withdrawal threshold (c: ChR2&ON vs ChR2&OFF P < 0.0001; ChR2&ON vs mCherry&ON P < 0.0001) and thermal paw withdrawal latency (d: ChR2&ON vs ChR2&OFF P = 0.0005; ChR2&ON vs mCherry&ON P = 0.0153) with (on) or without (off) optogenetic stimulation. Sham&ChR2, n = 8; Sham&mCherry, n = 9; SNI&ChR2, n = 9; SNI&mCherry, n = 6. e Experimental design of conditional place-preference (CPP) test (left) and quantification of CPP training (right). Sham&ChR2, n = 6; Sham&mCherry, n = 6; SNI&ChR2, n = 10; SNI&mCherry, n = 5. Sham&ChR2 P = 0.0470; SNI&ChR2 P = 0.0118. f Preference for sucrose in the SPT. Sham&ChR2, n = 6; Sham&mCherry, n = 6; SNI&ChR2, n = 7; SNI&mCherry, n = 5. P = 0.0094. h Schematic diagram of viral injection and drug delivery cannula implantation (left), and a representative trace showing depolarization of the hM3Dq-expressing neuron by CNO (right). i, j Effects of chemogenetic activation of VGluT3DRN neurons on the von Frey test in post-SNI 2W mice (i: P < 0.0001) and SPT in post-SNI 6W mice (j: ACSF&hM3Dq vs ACSF&mCherry P = 0.0035; Ketanserin&hM3Dq vs Ketanserin&mCherry P = 0.0473). hM3Dq, n = 7; mCherry, n = 6. Significance was assessed by two-way ANOVA followed by Bonferroni’s multiple comparisons test in (c, d, f, i, j) and two-tailed paired Student’s t-test in (e). All data are presented as the mean ± s.e.m except for (b) shown as box and whisker plots (medians, quartiles (boxes) and ranges minimum to maximum (whiskers)). *P < 0.05, **P < 0.01, ***P < 0.001, not significant (ns). Details of the statistical analyses are presented in Supplementary Data 1. Created with BioRender.com (b, h).

Back to article page