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. 2022 Aug 25;13:5010. doi: 10.1038/s41467-022-32742-x

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© The Author(s) 2022

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. 7 — a Effects of ZD7288 (intra-subicular injection, 500 nL) on the seizure stage, after-discharges durations (ADD), and generalized seizure durations (GSD) of sGS expression. N = 8, 7, and 9 mice, respectively. Kruskal–Wallis with post hoc Dunn’s test, *P < 0.05, ***P < 0.001 compared with Saline. b Effects of ZD7288 on the incidence of sGS. N = 8, 7, and 9 mice, respectively. Fisher’s exact test, **P < 0.01. c Left, scheme of experiments for viral expression in the ANT, EC and subiculum for conditional knockdown of HCN expression in ANT- and EC-projecting subicular neurons of wild-type mice. Right top, representative coronal image of mCherry florescence in the subiculum from a Sh-HCN1-mCherry ^ANT-SUB mouse. Right bottom, mCherry co-labeled with anti-HCN1, indicating the efficacy of knockdown. Scale bar, 25 μm. d Effects of HCN1 knockdown in a specific circuit on the development of seizure stage and ADD in hippocampal kindling model. Two-way repeated measures ANOVA post hoc Scheffe’s test, **P < 0.01, ShRNA-HCN1^ANT-SUB compared to mCherry; ##P < 0.01, ShRNA-HCN1^ANT-SUB compared to ShRNA-HCN1^EC-SUB. e Scheme of experiments for field excitatory postsynaptic potential (fEPSP) with single pulse test in the SUB-ANT circuit, and typical LFP recorded in the ANT during the test. f No differences were observed in test currents of the CaMKIIα-eGFP ^SUB-ANT-light (Control), CaMKIIα-Arch ^SUB-ANT-light (Arch), and CaMKIIα-eGFP ^{SUB ZD7288} (50 μM, 500 nL, ZD) groups. g Representative images of the single pulse response in the ANT in baseline and kindled state of three groups. Graphs of peak spike amplitude (h) and fEPSP slope (i) change in base and kindled states of three groups. One-way ANOVA with post hoc Dunnett’s test, ***P < 0.001, ****P < 0.0001 compared with control group. The number of mice used in each group is indicated in the figure. Data are presented as means ± SEM.