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. 2020 Jan 24;11:480. doi: 10.1038/s41467-019-13918-4

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© The Author(s) 2020

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. 5 — a Experimental design of the mouse study. CI-994 or DMSO was intraperitoneally injected. b Significant upregulation of Kcnk9 after CI-994 treatment in several brain regions normalized to DMSO treatment, Mann–Whitney U test. Regions from left to right, DMSO/CI-994, n = 12/13; 6/9; 12/14; 7/8; 9/12; 6/6; 9/9; 6/6; 7/8 and 7/4. c Upregulation of Kcnk9 in the cerebellum of CI-994-treated Kcnk9KO^mat mice (n = 13), but not of CI-994-treated WT mice (n = 12), each compared with DMSO-treated Kcnk9KO^mat (n = 12) and WT mice (n = 9). Two-way ANOVA and subsequent Bonferroni’s multiple comparisons test, ****P < 0.0001 (all comparisons except DMSO:WT vs. CI-994:WT). d RT-qPCR expression analysis of known genes in the imprinting cluster on mouse chromosome 15. CI-994 treatment (30 mg CI-994/kg body weight) did not affect expression of Trappc9, Peg13, Chrac1, and Eif2c2 in the hippocampus of Kcnk9KO^mat mice. Significant increase of Kcnk9 expression after CI-994 treatment, n = 5, P = 0.0079, Mann–Whitney U test. e Y-maze percentage alteration was examined for DMSO-treated WT mice (n = 20), CI-994-treated WT mice (n = 18), DMSO-treated Kcnk9KO^mat mice (n = 21) and CI-994 treated Kcnk9KO^mat (n = 24) mice. CI-994 or DMSO-treated WT mice and CI-994-treated Kcnk9KO^mat mice did not exhibit deficits in working memory. CI-994-treated Kcnk9KO^mat mice showed a significant increase in percent spontaneous alteration compared with DMSO-treated Kcnk9KO^mat mice. Two-way ANOVA, Tukey post hoc test, *P < 0.05, **P < 0.01. f Distance traveled in the home cage in light (12 h) phase (left section) and the dark (12 h) phase (right section). No differences between DMSO-treated WT (n = 20), CI-994-treated WT (n = 10), DMSO-treated Kcnk9KO^mat (n = 8) and CI-994-treated Kcnk9KO^mat (n = 9) mice in the distance traveled in the light phase were detected. DMSO-treated Kcnk9KO^mat (n = 12) mice displayed a significant increase of nocturnal activity compared with DMSO-treated WT mice (n = 24) and CI-994-treated Kcnk9KO^mat (n = 13) mice as well as a visible, but not significant increase of nocturnal activity compared with CI-994-treated WT mice (n = 15). Two-way ANOVA, Bonferroni’s post hoc test, **P < 0.01. b–f n = sample or data arising from biologically independent animals. e, f Behavioral experiments were performed in nine independent sessions. b–e Values are means ± SEM (±indicates the standard error). Statistical analyses and approaches are provided in Supplementary Table 1. Source data are provided as a Source Data file. The mouse image in this figure was created using Servier Medical Art templates, which are licensed under a Creative Commons Attribution 3.0 Unported License; https://smart.servier.com.