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. 2018 Oct 3;8:14765. doi: 10.1038/s41598-018-32516-w

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© The Author(s) 2018

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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Phase-response curve and period-response curve for medium exchange of circadian Bmal1 and Per2 rhythms in the adult SCN (a) Phase-responses in individual slices (n = 20) of circadian Bmal1 (green circle) and Per2 (red circle) rhythms in the adult SCN (upper). The SCN was pretreated with distilled water (see text). Mean phase-shifts with SD at CT0–CT6 (n = 5), CT6–CT12 (n = 4), CT12–CT18 (n = 5) and CT18–CT20 (n = 6) (lower). See also the legend for Fig. 4a. A significant phase-shift is indicated with asterisk (*). *p < 0.05, **p < 0.01, and a significant difference in the response between the two circadian rhythms is shown with dagger (^†). ^†p < 0.05. (b) Period-responses obtained from the same experiment as (a). Period-responses in individual slices of circadian Bmal1 (green circle) and Per2 (red circle) (upper), and the mean responses with SD at the 4 circadian phases (lower).