Figure 6.

TNFα downregulates GABAergic neurotransmission through PP1 but not PP2A. A, mIPSCs were recorded from control or TNFα-treated (100 ng/ml, 45 min) cultured neurons (preincubated with solvent alone or inhibitor). DMSO (0.1%) was used as a solvent for okadaic acid (OKA) and tautomycetin (TMT); DMF (0.1%) was used as a solvent for fostriecin (FOST). Shown are representative traces for control with DMSO preincubation, TNFα-treated with DMSO or DMF preincubation, TNFα-treated with okadaic acid preincubation (PP1/PP2A inhibitor, 0.5 μm), TNFα-treated with tautomycetin preincubation (PP1 inhibitor, 10 nm), and TNFα-treated with fostriecin preincubation (PP2A inhibitor, 10 nm). B, Group data of average mIPSC amplitudes for all conditions, showing that preincubation with okadaic acid or tautomycetin blocks the TNFα-induced downregulation of mIPSC amplitude, whereas preincubation with fostriecin does not (n = 16–25 cells in each condition; two-way ANOVA, Bonferroni's post hoc test, *p < 0.05, **p < 0.01, ***p < 0.001; n.s., not significant).