Fig. 5: Learning and memory dysfunction but not mood-related disorders were alleviated by the chemogenetic inhibition of the piriform cortex (PC) excitability neurons.

A Experimental timeline of virus injection for investigating the behavioral impact, CNO injections (3.3 mg/kg). B, C Schematic of the sagittal section of the mouse brain shows hM4D(Gi)-GFP virus injection. D Current-clamp recording of expressing hM4D(Gi) virus in the PC. The representative trace shows that PC neurons expressing hM4D(Gi) can be inhibited by bath application of 10 μM CNO. E The time spent in the novel arm following PC injections of AAV-GFP and AAV-hM4D(Gi) (F (2, 27) = 5.996, Con + GFP vs Sus + GFP: p = 0.002, Sus + GFP vs Sus + hM4Di: p = 0.035; One-way ANOVA). Con + GFP, injection with GFP-expressing viral vector in control mice, n = 10; Sus + GFP, injection with GFP-expressing viral vector in susceptible mice, n = 11; Sus + hM4Di, injection with hM4D(Gi)-expressing viral vector in susceptible mice, n = 9. F Escape latency (F (2, 27) = 1.878, p = 0.172; Two-way repeated measures ANOVA) and the time spent in the target quadrant (F (2, 27) = 4.209, Con + GFP vs Sus + GFP: p = 0.0402, Sus + GFP vs Sus + hM4Di: p = 0.0334; One-way ANOVA). Con + GFP, n = 10; Sus + GFP, n = 11; Sus + hM4Di, n = 9. G Representative animal trace of the open field test. H The time in the center (F (2,18) = 3.553, Con + GFP vs Sus + GFP: p = 0.0299, Sus + GFP vs Sus + hM4Di: p = 0.3182; One-way ANOVA) and the total distance did not change after the injection of CNO (F (2,18) = 3.696, Con + GFP vs Sus + GFP: p = 0.0631, Sus + GFP vs Sus + hM4Di: p = 0.3122; One-way ANOVA). Con + GFP, n = 6; Sus + GFP, n = 8; Sus + hM4Di, n = 7. I The hM4Di-susceptible mice presented no change in terms of both open arm exploration (x2 = 7.427, Con + GFP vs Sus + GFP: p = 0.0317, Sus + GFP vs Sus + hM4Di: p > 0.999; Kruskal–Wallis H) and entries into the open arm (F (2,18) = 4.654, Con + GFP vs Sus + GFP: p = 0.167, Sus + GFP vs Sus + hM4Di: p = 0.950; One-way ANOVA) compared to GFP-susceptible mice in the EPM test. Con + GFP, n = 6; Sus + GFP, n = 8; Sus + hM4Di, n = 7. J The immobility time in the forced swimming test (F (2, 18) = 3.186, Con + GFP vs Sus + GFP: p = 0.0494, Sus + GFP vs Sus + hM4Di: p = 0.8871; One-way ANOVA) and K tail suspension test (F (2,17) = 4.113, Con + GFP vs Sus + GFP: p = 0.0314, Sus + GFP vs Sus + hM4Di: p = 0.9842; One-way ANOVA). Con + GFP, n = 6, Sus + GFP, n = 8, Sus + hM4Di, n = 6. Data are presented as the mean ± SEM. *p < 0.05; **p < 0.01.