Fig. 7: Down-regulation of mGluR5 in ACC astrocytes decreases synaptic transmission, extracellular concentration of glutamate, and increases mechanical withdrawal threshold in CCI mice. | Communications Biology

Fig. 7: Down-regulation of mGluR5 in ACC astrocytes decreases synaptic transmission, extracellular concentration of glutamate, and increases mechanical withdrawal threshold in CCI mice.

From: mGluR5-mediated astrocytes hyperactivity in the anterior cingulate cortex contributes to neuropathic pain in male mice

Fig. 7: Down-regulation of mGluR5 in ACC astrocytes decreases synaptic transmission, extracellular concentration of glutamate, and increases mechanical withdrawal threshold in CCI mice.

a Representative traces of miniature excitatory postsynaptic currents (mEPSCs) recorded from layer II-III neurons of ACC in CCI (red), shRNA (blue) and scramble-shRNA (pink) mice. Summary of mEPSCs frequency (b, n = 6 cells from 3 CCI mice; n = 6 cells from 3 shRNA mice; n = 7 cells from 3 scramble-shRNA mice; CCI (red) = 2.072 ± 0.1933 Hz, shRNA (blue) = 1.189 ± 0.1084 Hz, scramble-shRNA (pink) = 2.407 ± 0.3412 Hz, p = 0.0096, F = 6.296, one-way ANOVA followed by Dunnett’s test) and amplitude (d, CCI (red) = 17.98 ± 1.892 pA, shRNA (blue) = 12.24 ± 1.219 pA, scramble-shRNA (pink) = 18.24 ± 1.410 pA, p = 0.0229, F = 4.829, one-way ANOVA followed by Dunnett’s test) in CCI, shRNA and scramble-shRNA mice. Cumulative probability plots of mEPSCs inter-event intervals (IEI) (c, CCI (red) vs. shRNA (blue), p < 0.0001, Kolmogorov-Smirnov test; CCI (red) vs. scramble-shRNA (pink), p = 0.4771, Kolmogorov-Smirnov Test) and mEPSCs amplitude (e, CCI (red) vs. shRNA (blue), p < 0.0001, Kolmogorov-Smirnov test; CCI (red) vs. scramble-shRNA (pink), p = 0.4006, Kolmogorov-Smirnov Test) in CCI, shRNA and scramble-shRNA mice. f Representative eEPSC traces evoked by pair pulse protocol (PPP) with an interval of 50 ms recorded in the ACC in CCI (red), shRNA (blue) and scramble-shRNA (pink) mice. g Summary bar graph of paired-pulse ratio (PPR) index (n = 7 cells from 7 CCI mice; n = 7 cells from 4 shRNA mice; n = 9 cells from 3 scramble-shRNA mice; CCI (red) = 0.9674 ± 0.04246, shRNA (blue) = 1.653 ± 0.3287, scramble-shRNA (pink) = 1.064 ± 0.1005, p = 0.0427, F = 3.709, one-way ANOVA followed by Dunnett’s test) of eEPSCs in CCI, shRNA and scramble-shRNA mice. h Extracellular glutamate concentrations in the dialysate in the ACC of CCI, shRNA and scramble-shRNA mice (n = 5 CCI mice; n = 7 shRNA mice; n = 6 scramble-shRNA mice; CCI (red) = 9.904 ± 0.9235 μM, shRNA (blue) = 5.033 ± 0.7157 μM, scramble-shRNA (pink) = 8.943 ± 0.8825 μM, p = 0.0017, F = 10.09, one-way ANOVA followed by Dunnett’s test). i Knockdown mGluR5 in ACC astrocytes significantly increased hind paw withdrawal threshold in neuropathic pain mice (n = 6 CCI mice; n = 7 shRNA mice; n = 11 scramble-shRNA mice; Day0_CCI (red circle) = 1.322 ± 0.07585 g, Day0_shRNA (blue circle) = 1.381 ± 0.1906 g, Day0_scramble-shRNA (pink circle) = 1.145 ± 0.1108 g, Day21_CCI (red circle) = 0.5972 ± 0.1801 g, Day21_shRNA (blue circle) = 1.522 ± 0.2658 g, Day21_scramble-shRNA (pink circle) = 0.4139 ± 0.08482 g; Day21_CCI vs. Day21_shRNA, p = 0.0011, Day21_CCI vs. Day21_scramble-shRNA, p = 0.5003, two-way ANOVA (F(2, 21) = 4.459, p = 0.0243), Tukey’s post hoc test). Error bars represent the mean ± SEM.

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