Fig. 4: PAGvGlut2 and RVMPenk neurons respectively contribute to SM1PAG and SM1RVM -mediated anti-nociception. | Nature Communications

Fig. 4: PAGvGlut2 and RVMPenk neurons respectively contribute to SM1PAG and SM1RVM -mediated anti-nociception.

From: Descending projection neurons in the primary sensorimotor cortex regulate neuropathic pain and locomotion in mice

Fig. 4

a Schematic of labeling strategy (left), and section of labeled PAGSM1 neurons (right). Scale bars, 200 μm. b–d RNAscope FISH showing colocalization (b) and proportion of vGlut2 (c) or vGat (d) mRNA with PAGSM1 neurons. Scale bars, 50 μm. e Schematic of recording configuration in vGlut2-cre mice. f Sample traces showing the SM1 terminals activating evoked oEPSC in PAGvGlut2 neurons, Blue arrow indicates optogenetic stimulation. g Schematic of SM1PAG activation combined with PAGvGlut2 inhibition. h and i Effects of inhibiting PAGvGlut2 on von Frey threshold (h P = 7.92 × 10−5) and Hargreaves latency (i P = 9.84 × 10−5). j Schematic of activating postsynaptic PAGvGlut2 neurons (left), and section of labeled PAGvGlut2 neurons (right). Scale bars, 200 μm. k Activating of postsynaptic PAGvGlut2 neurons increased the mechanical threshold (left, P = 0.0022) and thermal threshold (right, P = 0.0062) in CCI mice. l Schematic of labeling strategy (left), and section of labeled RVMSM1 neurons (right). Scale bars, 200 μm. m and n Immunofluorescence staining and RNAscope FISH showing colocalization (m) and proportion (n) of TPH, vGat and Penk mRNA with RVMSM1 neurons. Scale bars, 50 μm. o Proportion of Penk mRNA within vGat+ RVMSM1 neurons. p Schematic of recording configuration in Penk-cre mice. q Sample traces showing the SM1 terminals activating evoked oEPSC in RVMPenk neurons, Blue arrow indicates optogenetic stimulation. r Schematic of SM1RVM activation combined with RVMPenk inhibition. s and t Effects of inhibiting RVMPenk neurons on von Frey threshold (s P = 0.0001) and Hargreaves latency (t P = 0.0003). u Schematic of activating postsynaptic RVMPenk neurons. v Activating of postsynaptic RVMPenk neurons increased the mechanical threshold (left, P = 0.0195) and thermal threshold (right, P = 0.0003) in CCI mice. All data are expressed as mean ± sem, and (h, i, s, t) were analyzed by Brown-Forsythe ANOVA test or Kruskal-Wallis test followed by Dunn or Dunnett’s multiple comparisons test, (k and v) were analyzed by two-tailed unpaired t test or Mann Whitney test. Sample sizes are indicated in the figures, with detailed statistics provided in Supplementary Data 1. *P ≤ 0.05, **P ≤ 0.01. Source data are provided as a Source Data file.

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