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. 2021 Jul 22;11:14931. doi: 10.1038/s41598-021-94393-0

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© The Author(s) 2021

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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/.

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(A,B) Simulated dynamics of pERK, pRSK, p-p38 MAPK, PKAc, pCREB1, pCREB2_p38, NT, TBL and TGF-β levels after one or two 5-min pulses of 5-HT with ISI of 45 min, without block of TrkB (A), or with block of TrkB applied during both pulses of 5-HT (B). (A) Black solid curves, simulations after two pulses of 5-HT. Green curves, simulations after one pulse of 5-HT. Red arrows in A1 and A4 represent the overlapped increases of pERK and PKAc after two pulses of 5-HT. (B) Blue curves, simulations after two pulses with inhibitors; black dashed curves, control simulations without inhibitors, same as black solid curves in A. Numbers “1”, “2”, and “3” in A2, A5, A8, B2, B5, and B8 represent the waves or late shoulders of increase. Numbers “1”, and “2” in A3, A6, B3, and B6 represent the waves of decrease. (C) Empirical validation that TrkB Fc applied during both pulses of 5-HT suppressed the increase of pERK at 1 h post-onset of second pulse of 5-HT (n = 7). Data are represented as mean ± SEM. All scale bars are 40 μm. * p < 0.05.