Figure 8.

Abnormal network electrical spike activity (ESA) triggered by tetramethylenedisulfotetramine (TETS) is mitigated by the combination of midazolam (MDZ) and allopregnanolone (ALLO). A, ESA recordings were performed on 12 well microelectrode array plates consisting of 64 electrodes/well. B, Example of waveforms counted in ESA data capture using Axis software with the threshold set at 8 times the noise (faint gray trace in lower panel). C, Microelectrode array heat map shows the spatial distribution of ESA. D, Representative raster plots showing ESA activities before (Baseline) and after addition of TETS (1.0 μM) or TETS with the combination of MDZ (0.1 µM) and ALLO (0.1 µM). Summary data showing the influence of TETS, MDZ, and ALLO, singly or in combination, on Mean firing rate (E), mean burst frequency (F), and area under cross correlation—a measure of neuronal network synchronicity (G). ESA measures after TETS + drug additions are to their respective baseline periods before addition and statistically compared using ANOVA with Tukey post hoc correction. Mean ± SEM (n = 5–18 wells measured on 2–3 independent culture days). *p < .05; **p < .01; ***p < .001; and **** p < .0001.