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. 2024 Jan 16;17:1239069. doi: 10.3389/fncel.2023.1239069

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Copyright © 2024 Brown, Uy, Murtaza, Rosa, Alfonso, Dave, Kilpatrick, Cheng, White, Scherer and Singh.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Complete and partial loss of SCN2A impairs the development of spontaneous network activity via multi-electrode array. (A) Example raster plots of recordings of neuronal network activity at DIV 49 for CTRL-iso and SCN2A KO iNeurons. (B–G) Quantification of MEA parameters for CTRL-iso and KO iNeurons: (B) number of active electrodes [F(1, 83) = 35.55, p < 0.0001 for effect of genotype; F(5, 415) = 4.778, p = 0.0003 for interaction of time and genotype], (C) weighted mean firing rate [F(1, 83) = 37.31, p < 0.0001 for effect of genotype; F(5, 415) = 14.32, p < 0.0001 for interaction of time and genotype], (D) burst frequency [F(1, 83) = 27.78, p < 0.0001 for effect of genotype; F(5, 415) = 12.68, p < 0.0001 for interaction of time and genotype], (E) number of spikes per burst [F(1, 83) = 6.570, p = 0.0122 for effect of genotype; F(5, 415) = 5.011, p = 0.0002 for interaction of time and genotype], (F) number of spikes per network burst [F(1, 83) = 14.55, p = 0.0003 for effect of genotype; F(5, 415) = 11.85, p < 0.0001 for interaction of time and genotype], (G) synchrony index [F(1, 83) = 3.667, p = 0.0586 for effect of genotype; F(5, 415) = 4.170, p = 0.0010 for interaction of time and genotype]. CTRL-iso (n = 47 wells) and KO (n = 43 wells) iNeurons, 3 viral transductions. Data represent means ± SEM. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.001, two-way repeated measures ANOVA with post hoc Sidak correction. (H) Example raster plots of recordings of neuronal network activity at DIV 49 for CTRL-F1 and R607* iNeurons. (I–N) Quantification of MEA parameters for CTRL-F1 and R607* neurons: (I) number of active electrodes [F(2, 62) = 24.71, p < 0.0001 for effect of genotype; F(34, 1,054) = 18.50 = 4.778, p < 0.0001 for interaction of time and genotype], (J) weighted mean firing rate [F(1, 125) = 21.49, p < 0.0001 for effect of genotype; F(17, 2125) = 16.10, p < 0.0001 for interaction of time and genotype], (K) burst frequency [F(2, 62) = 8.794, p = 0.0004 for effect of genotype; F(34, 1,054) = 8.359, p < 0.0001 for interaction of time and genotype], (L) number of spikes per burst [F(2, 62) = 23.98, p < 0.0001 for effect of genotype; F(34, 1,054) = 17.17, p < 0.0001 for interaction of time and genotype], (M) number of spikes per network burst [F(2, 62) = 25.04, p < 0.0001 for effect of genotype; F(34, 1,054) = 15.83, p < 0.0001 for interaction of time and genotype], (N) synchrony index [F(2, 62) = 21.68, p < 0.0001 for effect of genotype; F(34, 1,054) = 18.94, p < 0.0001 for interaction of time and genotype]. CTRL-F1 (n = 48 wells) and R607* (n = 46 wells) iNeurons, 3 viral transductions. Data represent means ± SEM. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.001, two-way repeated measures ANOVA with post hoc Sidak correction.