Fig. 7: Weekly administration of D-cycloserine is optimal for rescuing social behavioral deficits in the KI mice.

A The flow chart of three-chamber/ electrophysiological tests for examining the rescue effect of DCS administration once a week for three consecutive weeks. B Representative heatmaps of the three-chamber tests performed in WT/KI mice one week after three consecutive weeks of saline/DCS administration. C DCS rescued social novelty deficits in the KI mice, as analyzed by the sociability difference index and the social novelty difference index, one week after three consecutive weeks of administration (two-way ANOVA, p = 0.400 [interaction], p = 0.575 [drug], and p = 0.382 [gene]; p = 0.037 [interaction], p = 0.275 [drug], and p = 0.047 [gene]; n in each bar, number of mice). See also Supplementary Fig. 5 for sniffing time. D Sample traces (left) and bar graph (right) of measurements of NMDA/AMPA receptor response ratios recorded from pyramidal neurons in the mPFC of P60-P70 mice one week after three consecutive weeks of DCS administration (two-way ANOVA, Interaction: F(1, 77) = 5.693, p = 0.020; Drug: F(1, 77) = 1.172, p = 0.282; WT vs. KI: F(1, 77) = 2.553, p = 0.114; n, number of neurons recorded from 4 saline-treated littermates and 4 DCS-treated littermates, respectively). E Top: Sample traces of averaged EPSCs recorded 5 min before (dark traces) and 25 min after (light traces) LTP induction. Below: Changes in EPSC amplitude induced by 100 Hz stimulation and quantification of EPSCs 25 min after stimulation compared to the respective values before stimulation in pyramidal neurons of the KI mice one week after three consecutive week administration of saline or D-cycloserine (Two-tailed Mann-Whitney test, p = 0.011; n in each bar, number of neurons recorded from 5 mice per group).All data were mean ± SEM. *p < 0.05.