OUP user menu

Stiff person syndrome-associated autoantibodies to amphiphysin mediate reduced GABAergic inhibition

Christian Geis, Andreas Weishaupt, Stefan Hallermann, Benedikt Grünewald, Carsten Wessig, Thomas Wultsch, Andreas Reif, Nadiya Byts, Marcus Beck, Sibylle Jablonka, Michael K. Boettger, Nurcan Üçeyler, Wernher Fouquet, Manfred Gerlach, Hans-Michael Meinck, Anna-Leena Sirén, Stephan J. Sigrist, Klaus V. Toyka, Manfred Heckmann, Claudia Sommer
Figure 8

(A) Whole-cell recording of granule cells (cell margins marked by dashed lines) in the hippocampal dentate gyrus showed only minor and not significant differences in amplitude or frequency of GABAergic miniature inhibitory postsynaptic currents when slices were pre-incubated with native-amphAB or control IgG (examples are averaged traces from single experiments; stim, stimulating electrode; rec, recording electrode; scale bar: 20 µm). (B) Analysis of mean inhibitory postsynaptic currents amplitudes during high frequency stimulation (10 Hz) showed significantly lower amplitudes in native-amphAB treated slices during the first phase of the train response (P < 0.001 for stimuli 10–20, P < 0.05 for stimuli 20–30) and in the recovery period (P < 0.05; native-amphAB: n = 7, control IgG: n = 10). Traces show averaged responses from two single experiments during train stimulation. After high-frequency stimulation, GABAergic inhibitory postsynaptic currents decline faster in native-amphAB treated cells compared with control IgG (τ = 0.9 s versus 1.7 s) and also the recovery of inhibitory postsynaptic currents amplitudes is substantially slower after the train stimulation (τ = 730 s versus 12 s).