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. Author manuscript; available in PMC: 2020 Jul 25.
Published in final edited form as: Science. 2019 Oct 11;366(6462):246–250. doi: 10.1126/science.aax5719

Fig. 4. Shisa7 KO diminishes DZ effects in vitro and in vivo.

Fig. 4.

(A) Shisa7, but not other molecules, potentiated the DZ effect on GABA response of α2β3γ2 in HEK cells (one-way ANOVA). Scale bar, 200 pA, 2 s. (B) Shisa7 KO significantly reduced DZ-induced potentiation of GABA-evoked whole-cell currents in cultured neurons (WT n = 24; KO n = 23; t test). Scale bar, 500 pA, 2 s. (C and D) DZ (1.5 mg/kg) increased the time spent on open arm and the number of open arm entries in WT mice but not Shisa7 KO mice. Veh, vehicle. (Treatment groups: Veh WT n = 14 and KO n = 21; DZ WT n = 10 and KO n = 15.) Time: treatment [F1,56 = 5.113, P < 0.05]; group [F1,56 = 0.016, P > 0.05]; treatment × group [F1,56 = 0.845, P > 0.05]; entries: treatment [F1,56 = 4.501, P < 0.05]; group [F1,56 = 0.035, P > 0.05]; treatment × group [F1,56 = 3.101, P > 0.05]; two-way ANOVA. (E) Dose-response relationship of DZ in LORR [Veh n = 6 for both conditions; DZ (3 mg/kg) n = 6 for both conditions; DZ (10 mg/kg) WT n = 6 for both conditions; DZ (30 mg/kg) WT n = 7, KO n = 6; DZ (50 mg/kg) WT n = 13 for both conditions). (F) DZ at the hypnotic dose produced LORR in 100% of WT mice (n = 13), but only 69% of KO mice (9 of 13 mice). (G) Shisa7 KO significantly prolonged latency to LORR and shortened duration of LORR after DZ administration (WT n = 13, KO n = 9; t test). Error bars indicate SEM. ****P < 0.0001; ***P < 0.001; **P < 0.01; *P < 0.05.