Fig. 7 FAE-20 increases hippocampal excitability and leads to more stable contextual fear memory in mice. FAE-20 increases hippocampal excitability and.

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Fig. 7 FAE-20 increases hippocampal excitability and leads to more stable contextual fear memory in mice. FAE-20 increases hippocampal excitability and leads to more stable contextual fear memory in mice. (A to D) Rhodiola extractcrude (A and B) or FAE-20 (C and D) was applied to acute murine hippocampal slices at the concentrations indicated, and the excitability of CA1 neurons was determined as the number of action potentials (APs) upon current injection. Excitability was increased by Rhodiola extractcrude [P < 0.05, two-way repeated-measures ANOVA (rmANOVA); n =10] and by FAE-20 [two-way rmANOVA with P > 0.05 for the two lower concentrations (n = 11 to 18) and P < 0.05 for the highest FAE-20 concentration (n = 13)], relative to the application of solvent as a control (n = 10 to 14). (E) Mice (3 months old) were intraperitoneally injected with either FAE-20 (6 mg/kg; n = 14) or solvent as a control (n = 13) 30 min before contextual fear conditioning training. On the next day, freezing behavior was tested in a novel context (to assess unspecific fear) and in the training context (to assess conditioned contextual fear). Animals from both groups discriminated equally well between the neutral and the training context (rmANOVA, all P values < 0.05). In control animals, contextual fear decreased over time [P < 0.05, Fisher’s least significant difference (LSD) post hoc test], yet memory remained stable upon FAE-20 treatment (P > 0.05) and was higher than that in control animals (P = 0.0007). (F) If animals were treated with a higher concentration of FAE-20, they again discriminated between the two contexts as well as control animals did (rmANOVA, all P values < 0.05). They showed a slight but statistically significant (P = 0.04) decline in freezing over time in the training context but, importantly, exhibited more freezing in the second half of the training context exposure than the control group (P < 0.0001), again indicating a more stable fear memory in FAE-20–treated mice (Fisher’s LSD post hoc comparisons; control, n = 13; FAE-20, n = 9). (G) As in (E), for 2.4- to 2.8-year-old mice. Animals from both groups discriminated equally well between the neutral and the training context (rmANOVA, all P values < 0.05). Animals treated with FAE-20 exhibited higher levels of fear memory in the training context (i.e., showed more freezing) than the control animals throughout the testing phase (P < 0.05, Fisher’s LSD post hoc test; control, n = 15; FAE-20, n = 16). Data are documented in data file S1. Birgit Michels et al. Sci Adv 2018;4:eaat6994 Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).