Extended Data Fig. 8: Chemogenetic inhibition of PV neurons masked emergence-induced neuronal hyperactivity.

a, Experimental timeline of CNO treatment and two-photon imaging of neuronal Ca²⁺ activity. WT, PV-GiDREADD⁺ mice or PLX treated PV-GiDREADD⁺ mice were infected with AAV9.CaMKII.GCaMP6s and AAV2-hSyn-DIO-hM4D(Gi)-mCherry. b, Representative image of PV^Cre/+ mice expressing Gi-DREADD (on PV neurons, mCherry) and GCaMP6 (on excitatory neurons). Scale bar: 50 μm. c, Representative traces of neuronal Ca²⁺ activity (∆F/F) with chemogenetic inhibition of PV neurons by CNO before, during and after anesthesia in 3 groups: WT-GiDREADD⁺ mice, PV-GiDREADD⁺ mice or PLX treated PV-GiDREADD⁺ mice. d–f, Neuronal Ca²⁺ signal amplitude (d), time active (e) and signal area (f) across experimental time points for WT-GiDREADD⁺ mice (n = 3 mice), PV-GiDREADD⁺ mice (n = 4 mice) or PLX treated PV-GiDREADD⁺ mice (n = 5 mice). p = 0.0024 (WT-GiDREADD⁺ mice versus PV-GiDREADD⁺ mice), p = 0.0003 (WT-GiDREADD⁺ mice versus PV-GiDREADD⁺ mice with PLX), F(2, 90) = 9.024 (d). p < 0.0001 (WT-GiDREADD⁺ mice versus PV-GiDREADD⁺ mice), p = 0.0032 (WT-GiDREADD⁺ mice versus PV-GiDREADD⁺ mice with PLX), F(2, 90) = 12.62 (e). p = 0.0044 (WT-GiDREADD⁺ mice versus PV-GiDREADD⁺ mice), p = 0.4894 (WT-GiDREADD⁺ mice versus PV-GiDREADD⁺ mice with PLX), F(2, 90) = 5.835 (f). Each dashed line indicates data from an individual mouse, while solid lines and error bars show the mean ± SEM. Two-way ANOVA followed by Tukey post-hoc test; n.s., not significant; **p < 0.01 and ****p < 0.0001.

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