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. 2019 Jun 10;9:166. doi: 10.1038/s41398-019-0495-5

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© The Author(s) 2019

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 4 — As seen in Cohort 1, a second independent cohort of Ts65Dn similarly displayed impaired spatial learning which was improved by training with distributed trials spaced at 1 h intervals. a WT successfully achieved the acquisition criterion of 15 s or less to reach the hidden platform location. No significance was detected in the time course for acquisition by WT mice trained with massed versus spaced trials (F_1,23 = 0.110, NS), indicating no faster learning in WT trained with spaced trials. A significant effect of training day was detected in WT (F_9,207 = 19.0, p < 0.001), indicating learning across days as expected. No significant interaction between massed versus spaced x training day was detected in WT (F_9,207 = 0.410, NS). b Ts65Dn did not achieve the acquisition criteria of 15 s or less to reach the hidden platform location. A significant difference was detected in the time course for acquisition by Ts65Dn mice trained with massed versus spaced trials (F_1,24 = 8.06, *p < 0.01), indicating faster learning with spaced training trials. A significant effect of training day was detected (F_9,216 = 5.60, p < 0.001), indicating some learning across training days. No significant interaction between massed versus spaced x training day was detected in Ts65Dn (F_9,216 = 1.02, NS). Three-way ANOVA detected significance for latency (F_1,9 = 23.1, p < 0.001), genotype (F_1,1 = 35.8, p < 0.001), no significance for latency x treatment (F_1,9 = 0.295, NS), or latency x genotype x treatment (F_1,9 = 1.11, NS). c–f Probe trial performance 24 h after the last training trial. c WT crossed the previously trained target platform location significantly more than over the corresponding left, right, and opposite locations, in both the massed and spaced training conditions (massed: F_3,48 = 6.85, *p < 0.001; Dunnett’s multiple comparisons adjusted p values: target vs. left p < 0.001, target vs. right p < 0.05, target vs. opposite p < 0.01; spaced: F_3,44 = 4.681, *p < 0.01; target vs. left p < 0.05, target vs. opposite p < 0.01. d Ts65Dn crossed the previously trained target platform location significantly more than the corresponding left, right, and opposite locations, after spaced training but not after massed training trials (massed: F_3,48 = 0.129, NS, spaced: F_3,48 = 4.64, *p < 0.01; target vs. left p < 0.05, target vs. right p < 0.05, target vs. opposite p < 0.01). e WT spent more time in the previously trained target quadrant than in the left, right, and opposite quadrants, for both massed versus spaced training groups (massed: F_3,48 = 12.5, *p < 0.001; target vs. left p < 0.001, target vs. right p < 0.001, target vs. opposite p < 0.001; spaced: F_3,44 = 6.45, *p < 0.001; target vs. left p < 0.001, target vs. right p < 0.05, target vs. opposite p < 0.01). f Ts65Dn spent more time in the previously trained target quadrant than in the left, right, and opposite quadrants, after spaced training but not after massed training trials (massed: F_3,48 = 2.32, NS; spaced: F_3,48 = 3.39, *p < 0.05; target vs. left p < 0.05, target vs. right p < 0.05)