Fig. 6: Metabolic rewiring affects glutamatergic synaptic transmission.

a Line graph indicating maximum current density at evoked voltages in control neurons with various DM-2OG treatments. Datapoint represents at least 5 independent samples, error = SD represented by shading. b Line graph indicating maximum current density at evoked voltages in patient neurons with various DM-2OG treatments. Datapoint represents at least 6 independent samples, error = SD represented by shading. c Representative averaged traces of spontaneous synaptic currents from single control (n events = 114) or patient (n events = 36) neurons in voltage-clamp. d Box plot of spontaneous synaptic event charge of individual neurons in voltage-clamp. P value is calculated via mann–whitney. e Over-representation analysis of top 10 up and down-regulated GO terms from untreated control (n = 5) and patient (n = 6) derived neurons. Count refers to number of contributing genes. f Volcano plot of differential regulation between untreated control (n = 5) and patient (n = 6) neurons. g Over-representation analysis of top 10 up- and down-regulated GO terms. Count refers to number of contributing genes from untreated control (n = 5) and 0.1 mM DM-2OG treated patient (n = 4) derived neurons. h Volcano plot of differential regulation between untreated control (n = 5) and 0.1 mM DM-2OG treated patient (n = 4) neurons. In (c, d), each datapoint represents one independent sample. Genotypes are control (blue) and patient (orange). In (a, b) centre is the mean and error are SD. In (c, e) colour represents P value magnitude. In (f, h) values are FDR, genes highlighted contribute to a top differentially regulated GO term. Dotted lines indicate Log2 fold change of 1 and -log10 P-value of 0.01. In (d), box plot is median and min/max. In panels (a–d), control is represented by Ct1 and Ct2, and patient is represented by Pt1 and Pt2. In panels (e–h), control is represented by Ct1.2 and Ct2, and patient is represented by Pt1.1, Pt1.2, Pt2.1, and Pt2.2.