Fig. 6: Decreasing the cofilin phosphorylation level in Ccny KO mice reverts the synaptic plasticity, spatial learning, and memory flexibility phenotypes observed in Ccny KO mice. | Molecular Psychiatry

Fig. 6: Decreasing the cofilin phosphorylation level in Ccny KO mice reverts the synaptic plasticity, spatial learning, and memory flexibility phenotypes observed in Ccny KO mice.

From: Cyclin Y regulates spatial learning and memory flexibility through distinct control of the actin pathway

Fig. 6

a, b Enhanced LTP in Ccny KO mice is reverted to WT control levels with the overexpression of cofilin-S3A-EGFP in the CA1 region of Ccny KO mice. a Data represent mean ± SEM of the peak EPSC amplitude relative to the baseline. LTP was induced by pairing stimulation (2 Hz for 90 s with 0 mV holding) at Schaffer collateral-CA1 synapses. n = 7, 6, 6, and 5 slices from 4 EGFP-overexpressing WT, 4 cofilin-S3A-EGFP-overexpressing WT, 4 EGFP-overexpressing Ccny KO, and 3 cofilin-S3A-EGFP-overexpressing Ccny KO mice, respectively. Representative evoked EPSC traces before (1) and after (2) LTP induction are shown. Scale bars, 50 pA and 40 ms. b Data represent mean ± SEM of evoked EPSC amplitudes during the last 5 min (35–40 min) of the recordings in (a). **P < 0.005, ***P < 0.0005, ns, not significant as indicated, one-way ANOVA followed by Tukey’s multiple comparisons test. c, d Weakened LTD in Ccny KO mice is restored to the WT control level with the overexpression of cofilin-S3A-EGFP in the CA1 region of Ccny KO mice. c Data represent mean ± SEM of the peak EPSC amplitude relative to the baseline. LTD was induced by a pairing protocol (5 Hz for 3 min with −40 mV holding) at Schaffer collateral-CA1 synapses. n = 6, 7, 5, and 7 slices from 4 mice in each of 4 experimental groups. Representative evoked EPSC traces before (1) and after (2) LTD induction are shown. Scale bars, 50 pA and 40 ms. d Data represent mean ± SEM of evoked EPSC amplitudes during the last 5 min (35–40 min) of the recordings in (c). *P < 0.05, **P < 0.005, ns, not significant as indicated, one-way ANOVA followed by Tukey’s multiple comparisons test. e–i Overexpression of cofilin-S3A-EGFP in Ccny KO mice slightly but significantly reduces spatial learning and memory. e Learning curve of latency to platform (zone) during the MWM task. Data represent mean ± SEM. *P < 0.05 as indicated, two-way ANOVA. f Travel distance to the platform zone during the probe test. ns, not significant, *P < 0.05 as indicated, Student’s unpaired t test. Bars on the left side of the dotted line are the averaged data of T1, T2, and T3. g, h Data represent mean ± SEM of the number of entries to (g) and time spent in (h) each quadrant during the probe test on Day 6. ns, not significant, *P < 0.05, **P < 0.005, ***P < 0.0005 compared to the TQ, Student’s unpaired t test. (i) The number of passing the platform zone during the probe test. ns, not significant as indicated, Student’s unpaired t test. j−m Overexpression of cofilin-S3A-EGFP in Ccny KO mice reduces memory flexibility in reversal learning of the MWM task. j Latency to platform (zone) during the reversal learning. Data represent mean ± SEM. *P < 0.05 as indicated, two-way ANOVA. k Travel distance to the platform zone during the reversal learning probe test. ns, not significant, Student’s unpaired t test. (l) Time spent in each quadrant during the reversal learning probe test. Data represent mean ± SEM. *P < 0.05 as indicated, Student’s unpaired t test. m The number of passing the platform zone during the reversal learning probe test. Data represent mean ± SEM. *P < 0.05 as indicated, Student’s unpaired t test. See also Supplementary Fig. S5.

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