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. 2022 Jul 15;5:709. doi: 10.1038/s42003-022-03667-4

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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. 4 — a, b RNA-sequencing was performed with hippocampal samples 1 week after repeated ketamine anesthesia or saline injections in male mice. a Volcano plot of DEGs, shown as blue (decreased expression) and red (increased expression) circles. b Gene ontology (GO) analysis of DEGs. Significant terms are highlighted in red (Axon initial segment, p < 0.001; Main axon, p = 0.007; Node of Ranvier, p = 0.034; n = 4 for each group). c–f Whole-cell recordings were performed 1 week after repeated ketamine anesthesia in hippocampal CA1 pyramidal neurons of male mice. c Enhanced intrinsic excitability after early repeated ketamine anesthesia. The number of action potentials was measured after injecting a series of depolarizing currents under current-clamp conditions (current injection = 60 pA, p = 0.034; 70 pA, p = 0.018; 80 pA, p = 0.006; 90 pA, p = 0.005; 100 pA, p = 0.009; 110 pA, p = 0.029; Student’s t test; control, n = 6 mice [total 20 cells]; anesthesia, n = 7 mice [total 20 cells]. d, e Altered excitatory and inhibitory spontaneous synaptic transmissions in hippocampal CA1 pyramidal neurons. d Anesthesia group showed increased frequency (Welch ANOVA, p = 0.039), but normal amplitude (Kruskal–Wallis test, p = 0.908) of sEPSCs (control, n = 7 mice [total 21 cells]; anesthesia, n = 8 mice [total 21 cells]). e Anesthesia group showed decreased frequency (Student’s t test, p = 0.010) but normal amplitude (Student’s t test, p = 0.418) of sIPSCs in hippocampal CA1 pyramidal neurons (control, n = 6 mice [total 22 cells]; anesthesia, n = 6 mice [total 22 cells]). f Spontaneous action potentials (sAP) are significantly increased after early repeated ketamine anesthesia. sAPs were measured under I = 0 mode (p = 0.010, Kruskal–Wallis test; Control, n = 6 mice [total 21 cells]; anesthesia, n = 6 mice [total 24 cells]). Values are presented as means ± SD (n.s., not significant; *p < 0.05; **p < 0.01).