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[Preprint]. 2024 Aug 28:2023.10.20.562785. Originally published 2023 Oct 23. [Version 2] doi: 10.1101/2023.10.20.562785

Figure 4. LC-mPFC MOR is crucial for intact LC-mediated antinociception.

Figure 4.

(A) Cartoon and fluorescent image illustrating the viral strategy for modular knockout of MOR in LC for electrophysiological recording. (B) Identification of LC-mPFC neurons with module-selective MOR knockout (mKO) by co-expression of mCherry. (C) Representative traces of cell-attached recording in LC neurons with an mKO neuron (bottom) showing a loss of DAMGO-mediated inhibition in spontaneous firing rate compared to a C57BL/6J control (top). (D) DAMGO-mediated inhibition of LC neurons is lost in mKO-targeted cells of Oprm1fl/fl mice. Student’s t-test, t = 5.033 *** p<0.001. (E) Schematic illustrating the viral strategy for modular knockout of MOR in LC-mPFC neurons for behavioral testing. (F) Timeline of longitudinal nociceptive measurements during the progressive Cre-mediated deletion of modular MOR in LC-mPFC projections. (G) von Frey test shows a significant decrease in 50% withdrawal threshold in mKO (Oprm1fl/fl::mPFC:CAV-PRS-Cre-V5) compared to Control (Oprm1fl/fl::mPFC:CAV-mCherry) mice. Repeated measures twoway ANOVA followed by Tukey’s posthoc test, F = 5.419 (modular KO); 4.516 (KO progress); 2.057 (interaction); 1.687 (animal), *p<0.05. (H) Baseline thermal withdrawal is also significantly decreased in thermal withdrawal threshold in mKO mice. Repeated measures two-way ANOVA followed by Tukey’s posthoc test, F = 3.062 (modular KO); 1.542 (KO progress); 7.140 (interaction); 2.973 (animal), *p<0.05; ** p<0.01; *** p<0.001. Data represented as mean ± SEM.