Fig. 2. Setd5^+/− cortical neurons trail wt counterparts in development of synchronized neural networks.

a Raster plots depict spontaneous firing activity in eight electrodes from a single well (wt, top; het, bottom) showing a qualitatively different firing pattern (scale bar 20 s). b Spontaneous spike activity is significantly reduced in het cells (genotype ****P < 10⁻⁴, F_1,341 = 22.37, DF = 1). c Synchrony index among het neurons lags significantly behind wt (genotype ***P < 10⁻³, F_1,379 = 12.86, DF = 1). d Example LFP trace after low-pass filtering raw MEA signal at 500 Hz. e, f Log₁₀ power ratio baselined to first day of MEA recording for low-frequency (1–10 Hz, e) and high-frequency/broadband gamma (100–150 Hz, f) power, with genotype-dependent differences in power ratio for high-frequency only [(entire time period: low-frequency F_1,45 = 0.55, P = 0.4644 and high-frequency F_1,45 = 10.17, **P = 0.0042); (6–11 DIV only: low-frequency F_1,11 = 18.91, **P = 0.0074 and high-frequency F_1,11 = 33.36, **P = 0.0022)]. g Example power spectral densities (PSD) from Setd5^+/+ (black) and Setd5^+/− (gray) cultures. Blue and yellow boxes denote low- and high-frequency regions of interest for (e) and (f), respectively. h Significantly reduced correlated firing activity among het neurons (****P < 10⁻⁴, t_1,12 = 10.65, DF = 8) measured by Ca²⁺ transients. Statistics: (b, c) n = neurons from 12 Setd5^+/+ and Setd5^+/− animals each; 2-way ANOVAs for factors genotype and DIV; replicates = individual wells (neurons from 1 animal/well) pooled from three separate experiments. (e, f) Replicates defined as data from neurons of individual animals, n = 8 Setd5^+/+ and n = 4 Setd5^+/−; 2-way ANOVAs for factors genotype and DIV. h n = neurons from five animals per genotype (583 Setd5^+/+ or 505 Setd5^+/− active total neurons), with each animal as a single replicate and t-test of group means. Error bars representing mean ± SEM