Fig. 3
ATX inhibition effectively reduced cortical hyperexcitability, PPI and hyperlocomotion in an animal model for schizophrenia. a Representative evoked field potentials of control and 10 µM HA130-treated slices before and after ketamine stimulation. Note the potentiation after ketamine application and the rescued field potentials after HA130 application on ketamine-treated slices. Dotted red lines depict control levels. b After an initial depression, ketamine application leads to a significant neuronal potentiation as shown by evoked field potential recordings (1 stimulation every 30 s; for amplitudes see Fig. S4B). However, ATX inhibition by HA130 significantly reduced ketamine potentiation back to baseline levels (n = 8 Ketamine and 7 Ketamine + HA130 (10 µM)-treated slices; two-way RM ANOVA and Bonferroni multiple comparison post hoc test). c Input/output (I/O) assessment of slopes using increasing stimulus intensities shows that HA130 application significantly decreased I/O-relationship (n = 6 Ketamine and 5 ketamine + HA130 (10 µM)-treated slices, two-way RM ANOVA and Bonferroni multiple comparison post hoc test; see also Fig. S4C). d Pre-pulse inhibition (PPI) was significantly reduced in ketamine-treated animals but restored to WT levels by ATX inhibition via in vivo application of PF8380. Startle amplitudes were not altered by ketamine application or by ATX inhibition (n = 13 control animals, 13 ketamine-treated animals and 16 ketamine + PF8380-treated animals; one-way ANOVA with Bonferroni’s multiple comparisons test; see also Fig. S4D) e Ketamine induced significant hyperlocomotion in an open field (OF) setting, whereas in vivo inhibition of ATX via PF8380 administration reduced ketamine-induced hyperlocomotion to WT levels (n = 14 control animals, 14 ketamine-treated animals and 15 ketamine + PF8380-treated animals; two-way RM ANOVA and Sidak’s multiple comparison post hoc test). Bars represent mean ± SEM. *p < 0.05, **p < 0.01, ***p < 0.001
