Fig 10. NMDAR activation rescues hyperactivity and NMDAR currents, but not anxiolytic-like behavior, in Ngl3−/−(Hyb) mice.
(A) DCS (20 mg/kg, intraperitoneal) or vehicle (saline), administered into the WT and Ngl3−/− mice 30 minutes before the test, rapidly rescues the hyperactivity of Ngl3−/− mice (2–3 months) without an effect on WT mice in the open-field test, as shown by the distance moved. n = 11 mice for WT-saline (V), 12 for WT-DCS (D), 13 for KO-V, and 15 for KO-D; *P < 0.05, ***P < 0.001, ns, not significant, two-way ANOVA with Bonferroni test. (B) DCS does not affect the anxiolytic-like behavior of Ngl3−/− mice (2–3 months) in the elevated plus maze test, as shown by time in open/closed arms. Note that the hyperactivity of Ngl3−/− mice on the elevated plus maze was not improved by DCS. n = 14 mice for WT-V, 12 for WT-D, 16 for KO-V, and 15 for KO-D; **P < 0.01, ***P < 0.001, ns, not significant, two-way ANOVA with Bonferroni test. (C) DCS rescues NMDAR function at SC-CA1 synapses of Ngl3−/− mice (P16–20), as shown by the NMDA/AMPA ratio. n = 10 slices from seven mice for WT-V; 8, 6 for WT-D; 10, 9 for KO-V; and 7, 5 for KO-D; *P < 0.05, ***P < 0.001, ns, not significant, two-way ANOVA with Bonferroni test. Primary data can be found in S3 Data. AMPA, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid; DCS, D-cycloserine; KO-D, knockout, drug; KO-V, knockout, vehicle; NMDA, N-methyl-D-aspartate; NMDAR, NMDA receptor; ns, not significant; SC-CA1, Schaffer collateral-CA1 pyramidal; WT, wild-type; WT-D, wild-type, drug; WT-V, wild-type, vehicle.