(A) Experimental design. Hippocampal neurons at DIV14 were treated with NVP (GluN2A-preferring antagonist NVP-AAM077, 100 nM), Ifen (GluN2B-preferring antagonist ifenprodil, 5 μM), or APV (broad-spectrum NMDAR antagonist, 100 μM) for 24 h and then recorded for tonic currents at DIV15.
(B) Ifen treatment increased tonic currents, whereas NVP treatment decreased tonic currents. n = 10–11 for each group, one-way ANOVA test, F(3,38) = 13.14, p < 0.0001 with Dunnett’s multiple comparisons test, Ctrl versus NVP, p = 0.031; Ctrl versus Ifen, p = 0.0023.
(C) Ifen treatment increased surface α5 expression, whereas NVP treatment decreased surface α5 expression. n = 33–43 for each group, Kruskal-Wallis test with Dunnett’s multiple comparisons test, Ctrl versus NVP, p = 0.0041; Ctrl versus Ifen, p = 0.0003.
(D) Endocytosis assay of α5-GABAARs in cultures. Surface α5-GABAARs (Sα5) were labeled in green, and internalized α5-GABAARs (Iα5) were in red. Bar graphs in the right showing that 24-h NVP treatment increased α5 internalization, whereas 24-h Ifen treatment decreased α5 internalization. n = 15–16 for each group, one-way ANOVA test, F(3,56) = 22.96, p < 0.0001 with Dunnett’s multiple comparisons test, Ctrl versus NVP: p = 0.0044; Ctrl versus Ifen: p < 0.0001.
*p < 0.05, **p < 0.01, ***p < 0.001, and ****p < 0.0001. All data are presented as mean ± SEM.
See also Figures S2 and S3.