Journal: Frontiers in Pharmacology
Article Title: Exposure to β-hydroxybutyrate reduces the operating set point and increases excitability in hippocampal circuitry of healthy mice
doi: 10.3389/fphar.2025.1557612
Figure Lengend Snippet: B-hydroxybutyrate effects on synaptic plasticity. (A) Long-term Potentiation (LTP) at CA1 induced by high frequency stimulation (HFS; 4 × 100 Hz) of Control (blue) and DHB slices (orange) (Control: 10 slices, 9 animals; DHB: 9 slices, 8 animals). DHB slices were 2 h treated with DHB (2 mM) before recordings. Time-course of field excitatory postsynaptic potential (fEPSP; slope), percentual change from baseline, plotted data are average ± SEM (Two-Way repeated measures ANOVA with Bonferroni posttest: DHB p = 0.0411; HFS response p < 0.0001, Interaction p = 0.0005). (B) Examples of Control and DHB fEPSP traces showing the magnitude of change from baseline (gray) and 60 min after HFS (black). (C) Violin plot of percentual field-EPSP (slope) after HFS at 15–20 min (176.5 ± 10.9 vs. 141.2 ± 9.4; unpaired t-test, p = 0.0262), 35–40 min (157.7 ± 12.2 vs. 132.0 ± 7.7; unpaired t-test, p = 0.0924) and 55–60 min (153.2 ± 13.7 vs. 120.3 ± 5.4; unpaired t-test, p = 0.0397) after HFS. (D) Magnitude of AMPAr excitatory postsynaptic current (EPSC) recorded from Control and slices exposed to 2 h DHB (2 mM). Plotted data are average from percentual change from minimal stimulation intensity (Control: 6 cells, 2 animals; DHB: 5 cells, 3 animals). The stimulation intensities are normalized with respect to the intensity value evocating the minimal response. Analysis showed no difference between Control and DHB group (Two-Way repeated measures ANOVA with Bonferroni posttest: DHB p = 0.6287; Stimulus intensity p < 0.0001, Interaction p = 0.8706). (E) Examples of AMPAr-EPSCs traces of Control and DHB group showing the amplitude with higher intensities of stimulation 100% (gray), 150% (dark gray) and 225% (black). (F) Magnitude of NMDAr excitatory postsynaptic current (EPSC) recorded from Control and slices exposed to 2 h DHB (2 mM). Plotted data are average from percentual change from minimal stimulation intensity (Control: 10 cells, 6 animals; DHB: 13 cells, 6 animals). The stimulation intensities are normalized with respect to the intensity value evocating the minimal response. Analysis showed no difference between Control and DHB group (Two-Way repeated measures ANOVA with Bonferroni post test: DHB p = 0.5477; Stimulus intensity p < 0.0001, Interaction p = 0.9446). (G) Examples of NMDAr-EPSCs traces of Control and DHB group showing the amplitude with higher intensities of stimulation 100% (gray), 150% (dark gray) and 225% (black).
Article Snippet: To evaluate intrinsic excitability, extra synaptic blockers were added to aCSF before current steps: selective and non-competitive NMDAr antagonist (50 μm, MK-801; Tocris, Cat. No. 0924); AMPA/Kainate Glutamate receptor antagonist (10 μm, DNQX; Tocris: Cat. No. 0189); GABA A receptor antagonist (50 μM, PTX; Tocris: Cat. No. 1128).
Techniques: Control
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