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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 neonatal SCN (a) Phase-responses in individual slices (n = 22) of circadian Bmal1 (green circle) and Per2 (red circle) rhythms in the neonatal SCN (upper). The abscissa indicates the circadian phase in CT, where CT1 is the peak phase of Bmal1 rhythm and the ordinate indicates phase-shifts in hours with a positive sign for phase-advance shifts and with a negative for phase-delay. Mean phase-shifts with SD at CT0–CT6 (n = 5), CT6–CT12 (n = 9), CT12–CT18 (n = 4) and CT18–CT20 (n = 5) (lower). A significant phase-shift is indicated with asterisk (*) and a significant difference between the phase-shifts of two circadian rhythms is shown with dagger (^†). **p < 0.01 (one-way repeated measure ANOVA), ^‡p < 0.01 (two-way repeated measure ANOVA with post hoc Tukey-Kramer test). (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).