Fig. 5: Differential alterations of the excitation to inhibition balance in ion currents of microtransplanted receptors from AD and DS parietal cortex.

a Functional responses of microtransplanted synaptic receptors were elicited by application of 1 mM GABA, 100 µM kainate (Kai), or 10 μM s-AMPA in combination with 10 μM cyclothiazide (CTZ), after 3 min preincubation with CTZ. b No significant group differences were found in the maximal amplitude of agonist-induced ion currents for any of the responses (non-parametric Wilcoxon test P = 0.13 for kainate, P = 0.08 for AMPA + CTZ, P = 0.18 for GABA; n = 5 controls, 5 AD and 6 DS). P values in each plot are from two-sided Dunn’s post hoc rank test comparing groups versus control. The DS group had both the largest, and some of the smallest, responses indicating a large within-group data spread in this condition. c Kainate-induced responses were not potentiated by concanavalin A (Con-A), a positive allosteric modulator specific for kainate-type glutamate receptors, and did not show differences between groups (one way ANOVA (F (2,11) = 0.66, P = 0.5; n = 5 controls, 5 DS and 4 AD), indicating that the participation of kainate receptors is negligible and kainate-induced receptors are generated by AMPA-type receptors. d,e Plots showing the correlation between the maximum amplitude responses of excitatory receptors activated by kainate or AMPA plus CTZ and those of inhibitory receptors activated by GABA. Each point represents the average of responses from multiple independent recordings in oocytes from 7 frogs. For the exact number of oocytes per subject in all MSM experiments see Supplementary Data 2. The solid lines represent the Pearson’s correlation. f Excitation to inhibition ratio, defined as the average of maximum amplitude of kainate- to GABA-induced currents measured from the same oocyte was significantly larger in oocytes microtransplanted with synaptic membranes from AD compared to control brains (F (2,13) = 4.3, P = 0.037; n = 5 controls, 5 AD and 6 DS). P values in plot are from two-sided Dunnett’s post hoc test comparing groups versus control. For all box plots, the median in each group is represented by the line within the box, and the first and third quartiles are represented by the ends of the box. The whiskers extend from each end of the box to the first or third quartile ±1.5 (interquartile range). Outliers are represented beyond the whiskers.