Fig. 6: Long-term rescue effects of D-Cycloserine on mPFC deficits and social behaviors in NL3 R451C KI mice. | Communications Biology

Fig. 6: Long-term rescue effects of D-Cycloserine on mPFC deficits and social behaviors in NL3 R451C KI mice.

From: Social memory engram formation impairment in neuroligin-3 R451C knock-in mice is caused by disrupted prefrontal NMDA receptor-dependent potentiation

Fig. 6

A The flowchart of electrophysiological tests for examining of rescue effect three days after D-cycloserine administration. Sample traces (B) and bar graph (C) of measurements of NMDA/AMPA receptor response ratios recorded from pyramidal neurons in the mPFC of P60-P70 mice three days after one-dose saline or D-cycloserine administration (two-way ANOVA, Interaction: F(1, 81) = 1.228, p = 0.271; Drug: F(1, 81) = 4.355, p = 0.040; WT vs. KI: F(1, 81) = 5.658, p = 0.020; n, number of neurons recorded from 4 saline-treated littermates and 4 DCS-treated littermates, respectively). D 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 three days after one-dose administration of saline or D-cycloserine (Two-tailed unpaired t test, t = 2.135, df = 20, p = 0.045; n in each bar, number of neurons recorded from 4 saline-treated KI mice and 8 DCS-treated KI mice, respectively). E The flow chart of three-chamber/electrophysiological tests for examining the rescue effect one week or three weeks after D-cycloserine administration. F–I Representative heatmaps (F and H) and statistical bar charts (G and I) illustrating the results of the three-chamber social interaction tests conducted in WT/KI mice, one or three weeks following a single administration of Saline/DCS (two-way ANOVA. For one-week data, p = 0.736 [interaction], p = 0.139 [drug], and p = 0.596 [gene]; p = 0.008 [interaction], p = 0.324 [drug], and p = 0.083 [gene]; for three-week data, p = 0.985 [interaction], p = 0.077 [drug], and p = 0.521 [gene]; p = 0.575 [interaction], p = 0.657 [drug], and p < 0.0001 [gene]; n in each bar, number of mice). See also Supplementary Fig. 4 for sniffing time. J 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 or three weeks after a single dose D-cycloserine administration (two-way ANOVA, Interaction: F(1, 58) = 8.930, p = 0.004; 1w vs. 3w: F(1, 58) = 4.197, p = 0.045; WT vs. KI: F(1, 58) = 2.228, p = 0.141; n, number of neurons recorded from 4 littermates treated with DCS for 1 week and 4 littermates treated with DCS for 3 weeks, respectively). K Top: Sample traces of averaged EPSCs recorded 5 minutes 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 minutes after stimulation compared to the respective values before stimulation in pyramidal neurons of the KI mice one week or three weeks after a single dose administration of D-cycloserine (Two-tailed unpaired t test, t = 2.729, df = 12, p = 0.018; n in each bar, number of neurons recorded from 5 mice per group).All data were mean ± SEM. *p < 0.05, **p < 0.01, ***p < 0.001.

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